Carrel name: keyword-zikv-cord Creating study carrel named keyword-zikv-cord Initializing database file: cache/cord-002341-v4r5d26a.json key: cord-002341-v4r5d26a authors: Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung title: Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons date: 2016-11-12 journal: EBioMedicine DOI: 10.1016/j.ebiom.2016.11.017 sha: doc_id: 2341 cord_uid: v4r5d26a file: cache/cord-002164-oqc9h2lu.json key: cord-002164-oqc9h2lu authors: Kumar, Ashutosh; Singh, Himanshu N.; Pareek, Vikas; Raza, Khursheed; Dantham, Subrahamanyam; Kumar, Pavan; Mochan, Sankat; Faiq, Muneeb A. title: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome date: 2016-08-09 journal: Front Hum Neurosci DOI: 10.3389/fnhum.2016.00403 sha: doc_id: 2164 cord_uid: oqc9h2lu file: cache/cord-002247-e0z5ypii.json key: cord-002247-e0z5ypii authors: Squires, Raynal C; Konings, Frank title: Preparedness for Zika virus testing in the World Health Organization Western Pacific Region date: 2016-03-31 journal: Western Pac Surveill Response J DOI: 10.5365/wpsar.2016.7.1.007 sha: doc_id: 2247 cord_uid: e0z5ypii file: cache/cord-002720-lrkscs71.json key: cord-002720-lrkscs71 authors: Kurosaki, Yohei; Martins, Danyelly Bruneska Gondim; Kimura, Mayuko; Catena, Andriu dos Santos; Borba, Maria Amélia Carlos Souto Maior; Mattos, Sandra da Silva; Abe, Haruka; Yoshikawa, Rokusuke; de Lima Filho, José Luiz; Yasuda, Jiro title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date: 2017-10-18 journal: Sci Rep DOI: 10.1038/s41598-017-13836-9 sha: doc_id: 2720 cord_uid: lrkscs71 file: cache/cord-002581-r7mskri0.json key: cord-002581-r7mskri0 authors: Magnani, Diogo M.; Silveira, Cassia G. T.; Rosen, Brandon C.; Ricciardi, Michael J.; Pedreño-Lopez, Núria; Gutman, Martin J.; Bailey, Varian K.; Maxwell, Helen S.; Domingues, Aline; Gonzalez-Nieto, Lucas; Avelino-Silva, Vivian I.; Trindade, Mateus; Nogueira, Juliana; Oliveira, Consuelo S.; Maestri, Alvino; Felix, Alvina Clara; Levi, José Eduardo; Nogueira, Mauricio L.; Martins, Mauricio A.; Martinez-Navio, José M.; Fuchs, Sebastian P.; Whitehead, Stephen S.; Burton, Dennis R.; Desrosiers, Ronald C.; Kallas, Esper G.; Watkins, David I. title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus date: 2017-06-12 journal: PLoS Negl Trop Dis DOI: 10.1371/journal.pntd.0005655 sha: doc_id: 2581 cord_uid: r7mskri0 file: cache/cord-003187-qdbcdn2j.json key: cord-003187-qdbcdn2j authors: Bassi, Maria Rosaria; Sempere, Raquel Navarro; Meyn, Prashansa; Polacek, Charlotta; Arias, Armando title: Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs date: 2018-08-27 journal: Antimicrob Agents Chemother DOI: 10.1128/aac.00380-18 sha: doc_id: 3187 cord_uid: qdbcdn2j file: cache/cord-002754-xlk4xpv2.json key: cord-002754-xlk4xpv2 authors: Mögling, Ramona; Zeller, Hervé; Revez, Joana; Koopmans, Marion; Reusken, Chantal title: Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016 date: 2017-09-07 journal: Euro Surveill DOI: 10.2807/1560-7917.es.2017.22.36.30609 sha: doc_id: 2754 cord_uid: xlk4xpv2 file: cache/cord-003041-v9uevz3l.json key: cord-003041-v9uevz3l authors: Zukor, Katherine; Wang, Hong; Siddharthan, Venkatraman; Julander, Justin G.; Morrey, John D. title: Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice date: 2018-02-23 journal: J Neurovirol DOI: 10.1007/s13365-017-0595-z sha: doc_id: 3041 cord_uid: v9uevz3l file: cache/cord-003284-hjx2d5rq.json key: cord-003284-hjx2d5rq authors: Márquez-Jurado, Silvia; Nogales, Aitor; Ávila-Pérez, Ginés; Iborra, Francisco J.; Martínez-Sobrido, Luis; Almazán, Fernando title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date: 2018-10-07 journal: Viruses DOI: 10.3390/v10100547 sha: doc_id: 3284 cord_uid: hjx2d5rq file: cache/cord-003403-ypefqm71.json key: cord-003403-ypefqm71 authors: Roberts, Christine C.; Maslow, Joel N. title: Assay Challenges for Emerging Infectious Diseases: The Zika Experience date: 2018-10-02 journal: Vaccines (Basel) DOI: 10.3390/vaccines6040070 sha: doc_id: 3403 cord_uid: ypefqm71 file: cache/cord-003453-p2buyrcj.json key: cord-003453-p2buyrcj authors: Batista, Mariana N.; Braga, Ana Cláudia S.; Campos, Guilherme Rodrigues Fernandes; Souza, Marcos Michel; de Matos, Renata Prandini Adum; Lopes, Tairine Zara; Candido, Natalia Maria; Lima, Maria Leticia Duarte; Machado, Francielly Cristina; de Andrade, Stephane Tereza Queiroz; Bittar, Cíntia; Nogueira, Maurício L.; Carneiro, Bruno M.; Mariutti, Ricardo B.; Arni, Raghuvir Krishnaswamy; Calmon, Marilia Freitas; Rahal, Paula title: Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date: 2019-01-11 journal: Viruses DOI: 10.3390/v11010049 sha: doc_id: 3453 cord_uid: p2buyrcj file: cache/cord-003482-f1uvohf0.json key: cord-003482-f1uvohf0 authors: Malmlov, Ashley; Bantle, Collin; Aboellail, Tawfik; Wagner, Kaitlyn; Campbell, Corey L.; Eckley, Miles; Chotiwan, Nunya; Gullberg, Rebekah C.; Perera, Rushika; Tjalkens, Ronald; Schountz, Tony title: Experimental Zika virus infection of Jamaican fruit bats (Artibeus jamaicensis) and possible entry of virus into brain via activated microglial cells date: 2019-02-04 journal: PLoS Negl Trop Dis DOI: 10.1371/journal.pntd.0007071 sha: doc_id: 3482 cord_uid: f1uvohf0 file: cache/cord-004053-nmt221tu.json key: cord-004053-nmt221tu authors: Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N. title: Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity date: 2019-11-06 journal: Biomolecules DOI: 10.3390/biom9110710 sha: doc_id: 4053 cord_uid: nmt221tu file: cache/cord-004418-08dljap3.json key: cord-004418-08dljap3 authors: Young, Ginger; Bohning, Kelly J.; Zahralban-Steele, Melissa; Hather, Greg; Tadepalli, Sambasivarao; Mickey, Kristen; Godin, C. Steven; Sanisetty, Srisowmya; Sonnberg, Stephanie; Patel, Hetal K.; Dean, Hansi J. title: Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date: 2020-02-26 journal: Sci Rep DOI: 10.1038/s41598-020-60415-6 sha: doc_id: 4418 cord_uid: 08dljap3 file: cache/cord-009399-6zpkpdzu.json key: cord-009399-6zpkpdzu authors: Sun, Fang; Xia, Zhiqiang; Han, Yuewen; Gao, Minjun; Wang, Luyao; Wu, Yingliang; Sabatier, Jean-Marc; Miao, Lixia; Cao, Zhijian title: Topology, Antiviral Functional Residues and Mechanism of IFITM1 date: 2020-03-08 journal: Viruses DOI: 10.3390/v12030295 sha: doc_id: 9399 cord_uid: 6zpkpdzu file: cache/cord-004020-qtwcbn7m.json key: cord-004020-qtwcbn7m authors: Gao, Yaning; Tai, Wanbo; Wang, Ning; Li, Xiang; Jiang, Shibo; Debnath, Asim K.; Du, Lanying; Chen, Shizhong title: Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date: 2019-11-02 journal: Viruses DOI: 10.3390/v11111019 sha: doc_id: 4020 cord_uid: qtwcbn7m file: cache/cord-004022-cr0zskcw.json key: cord-004022-cr0zskcw authors: Lu, Chien-Yi; Lin, Chen-Sheng; Lai, Hsueh-Chou; Yu, Ya-Wen; Liao, Chih-Yi; Su, Wen-Chi; Ko, Bo-Han; Chang, Young-Sheng; Huang, Su-Hua; Lin, Cheng-Wen title: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date: 2019-10-31 journal: Viruses DOI: 10.3390/v11111005 sha: doc_id: 4022 cord_uid: cr0zskcw file: cache/cord-102612-xx5l8r9e.json key: cord-102612-xx5l8r9e authors: Kodani, Andrew; Knopp, Kristeene A.; Di Lullo, Elizabeth; Retallack, Hanna; Kriegstein, Arnold R.; DeRisi, Joseph L.; Reiter, Jeremy F. title: Zika virus alters centrosome organization to suppress the innate immune response date: 2020-09-15 journal: bioRxiv DOI: 10.1101/2020.09.15.298083 sha: doc_id: 102612 cord_uid: xx5l8r9e file: cache/cord-016796-g4kqqpy1.json key: cord-016796-g4kqqpy1 authors: Bramhachari, Pallaval Veera; Mohana Sheela, Ganugula; Prathyusha, A. 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N.; Madhavi, M.; Satish Kumar, K.; Reddy, Neelapu Nageswara Rao; Berde, Chanda Parulekar title: Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges date: 2019-11-05 journal: Dynamics of Immune Activation in Viral Diseases DOI: 10.1007/978-981-15-1045-8_17 sha: doc_id: 16796 cord_uid: g4kqqpy1 file: cache/cord-102796-rr8qet8c.json key: cord-102796-rr8qet8c authors: Counotte, Michel J; Meili, Kaspar W; Low, Nicola title: Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak date: 2020-03-18 journal: nan DOI: 10.1101/2020.03.16.20036806 sha: doc_id: 102796 cord_uid: rr8qet8c file: cache/cord-260336-kwzo8puo.json key: cord-260336-kwzo8puo authors: Si, Lulu; Meng, Yu; Tian, Fang; Li, Weihua; Zou, Peng; Wang, Qian; Xu, Wei; Wang, Yuzhu; Xia, Minjie; Hu, Jingying; Jiang, Shibo; Lu, Lu title: A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue date: 2019-09-27 journal: Front Microbiol DOI: 10.3389/fmicb.2019.02250 sha: doc_id: 260336 cord_uid: kwzo8puo file: cache/cord-102279-ena1usqv.json key: cord-102279-ena1usqv authors: Long, Rory K. 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Wayne; Jean, François; Hamarneh, Ghassan; Nabi, Ivan R. title: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date: 2020-06-23 journal: bioRxiv DOI: 10.1101/2020.05.12.091611 sha: doc_id: 102279 cord_uid: ena1usqv file: cache/cord-263868-ewnf96cz.json key: cord-263868-ewnf96cz authors: Srivastava, Mayank; Zhang, Ying; Chen, Jian; Sirohi, Devika; Miller, Andrew; Zhang, Yang; Chen, Zhilu; Lu, Haojie; Xu, Jianqing; Kuhn, Richard J.; Andy Tao, W. title: Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor date: 2020-08-04 journal: Nat Commun DOI: 10.1038/s41467-020-17638-y sha: doc_id: 263868 cord_uid: ewnf96cz file: cache/cord-257539-01s21vh0.json key: cord-257539-01s21vh0 authors: Delvecchio, Rodrigo; Higa, Luiza M.; Pezzuto, Paula; Valadão, Ana Luiza; Garcez, Patrícia P.; Monteiro, Fábio L.; Loiola, Erick C.; Dias, André A.; Silva, Fábio J. 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Parveen, Shama title: Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future date: 2017-08-04 journal: Intervirology DOI: 10.1159/000478729 sha: doc_id: 272405 cord_uid: jmwn8pdn file: cache/cord-278286-1xk31726.json key: cord-278286-1xk31726 authors: Mutso, Margit; St John, James A.; Ling, Zheng Lung; Burt, Felicity J.; Poo, Yee Suan; Liu, Xiang; Žusinaite, Eva; Grau, Georges E.; Hueston, Linda; Merits, Andres; King, Nicholas J.C.; Ekberg, Jenny A.K.; Mahalingam, Suresh title: Basic insights into Zika virus infection of neuroglial and brain endothelial cells date: 2020-04-30 journal: J Gen Virol DOI: 10.1099/jgv.0.001416 sha: doc_id: 278286 cord_uid: 1xk31726 file: cache/cord-273065-peqz7okh.json key: cord-273065-peqz7okh authors: Girard, Marc; Nelson, Christopher B.; Picot, Valentina; Gubler, Duane J. title: Arboviruses: A global public health threat date: 2020-04-24 journal: Vaccine DOI: 10.1016/j.vaccine.2020.04.011 sha: doc_id: 273065 cord_uid: peqz7okh file: cache/cord-292830-gcfx1095.json key: cord-292830-gcfx1095 authors: Ianevski, Aleksandr; Zusinaite, Eva; Kuivanen, Suvi; Strand, Mårten; Lysvand, Hilde; Teppor, Mona; Kakkola, Laura; Paavilainen, Henrik; Laajala, Mira; Kallio-Kokko, Hannimari; Valkonen, Miia; Kantele, Anu; Telling, Kaidi; Lutsar, Irja; Letjuka, Pille; Metelitsa, Natalja; Oksenych, Valentyn; Bjørås, Magnar; Nordbø, Svein Arne; Dumpis, Uga; Vitkauskiene, Astra; Öhrmalm, Christina; Bondeson, Kåre; Bergqvist, Anders; Aittokallio, Tero; Cox, Rebecca J.; Evander, Magnus; Hukkanen, Veijo; Marjomaki, Varpu; Julkunen, Ilkka; Vapalahti, Olli; Tenson, Tanel; Merits, Andres; Kainov, Denis title: Novel activities of safe-in-human broad-spectrum antiviral agents date: 2018-04-23 journal: Antiviral Res DOI: 10.1016/j.antiviral.2018.04.016 sha: doc_id: 292830 cord_uid: gcfx1095 file: cache/cord-262944-9k64f0tw.json key: cord-262944-9k64f0tw authors: Parker, Elaine L.; Silverstein, Rachel B.; Verma, Sonam; Mysorekar, Indira U. title: Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date: 2020-10-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.522047 sha: doc_id: 262944 cord_uid: 9k64f0tw file: cache/cord-273326-gmw8gl2r.json key: cord-273326-gmw8gl2r authors: Saiz, Juan-Carlos; de Oya, Nereida Jiménez; Blázquez, Ana-Belén; Escribano-Romero, Estela; Martín-Acebes, Miguel A. title: Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date: 2018-08-24 journal: Viruses DOI: 10.3390/v10090453 sha: doc_id: 273326 cord_uid: gmw8gl2r file: cache/cord-300459-tu2xrt9x.json key: cord-300459-tu2xrt9x authors: Li, Cui; Gao, Fei; Yu, Lei; Wang, Ruoke; Jiang, Yisheng; Shi, Xuanling; Yin, Chibiao; Tang, Xiaoping; Zhang, Fuchun; Xu, Zhiheng; Zhang, Linqi title: A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos date: 2018-05-01 journal: Cell Rep DOI: 10.1016/j.celrep.2018.04.005 sha: doc_id: 300459 cord_uid: tu2xrt9x file: cache/cord-298166-045evk7g.json key: cord-298166-045evk7g authors: Röcker, Annika E.; Müller, Janis A.; Dietzel, Erik; Harms, Mirja; Krüger, Franziska; Heid, Christian; Sowislok, Andrea; Riber, Camilla Frich; Kupke, Alexandra; Lippold, Sina; von Einem, Jens; Beer, Judith; Knöll, Bernd; Becker, Stephan; Schmidt-Chanasit, Jonas; Otto, Markus; Vapalahti, Olli; Zelikin, Alexander N.; Bitan, Gal; Schrader, Thomas; Münch, Jan title: The molecular tweezer CLR01 inhibits Ebola and Zika virus infection date: 2018-02-08 journal: Antiviral Res DOI: 10.1016/j.antiviral.2018.02.003 sha: doc_id: 298166 cord_uid: 045evk7g file: cache/cord-330743-o11d0aa1.json key: cord-330743-o11d0aa1 authors: Yu, Xi; Zhang, Liming; Tong, Liangqin; Zhang, Nana; Wang, Han; Yang, Yun; Shi, Mingyu; Xiao, Xiaoping; Zhu, Yibin; Wang, Penghua; Ding, Qiang; Zhang, Linqi; Qin, Chengfeng; Cheng, Gong title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date: 2020-05-25 journal: bioRxiv DOI: 10.1101/2020.05.22.109900 sha: doc_id: 330743 cord_uid: o11d0aa1 file: cache/cord-332473-ec8lu2a3.json key: cord-332473-ec8lu2a3 authors: Amorim, Raquel; Temzi, Abdelkrim; Griffin, Bryan D.; Mouland, Andrew J. title: Zika virus inhibits eIF2α-dependent stress granule assembly date: 2017-07-17 journal: PLoS Negl Trop Dis DOI: 10.1371/journal.pntd.0005775 sha: doc_id: 332473 cord_uid: ec8lu2a3 file: cache/cord-319781-6thdg2up.json key: cord-319781-6thdg2up authors: Payne, Kelly; Kenny, Peter; Scovell, Jason M.; Khodamoradi, Kajal; Ramasamy, Ranjith title: Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men date: 2020-07-24 journal: Sex Med Rev DOI: 10.1016/j.sxmr.2020.06.003 sha: doc_id: 319781 cord_uid: 6thdg2up file: cache/cord-321312-hgp2jwbl.json key: cord-321312-hgp2jwbl authors: Carvalho, Sandhra M.; Mansur, Alexandra A.P.; Carvalho, Isadora C.; Costa, Érica A.; Guedes, Maria Isabel M.C.; Kroon, Erna G.; Lobato, Zelia I.P.; Mansur, Herman S. title: Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions date: 2020-07-10 journal: Mater Lett DOI: 10.1016/j.matlet.2020.128279 sha: doc_id: 321312 cord_uid: hgp2jwbl file: cache/cord-300379-db79kb5c.json key: cord-300379-db79kb5c authors: Park, Jun-Gyu; Ávila-Pérez, Ginés; Madere, Ferralita; Hilimire, Thomas A.; Nogales, Aitor; Almazán, Fernando; Martínez-Sobrido, Luis title: Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid date: 2019-04-12 journal: Front Microbiol DOI: 10.3389/fmicb.2019.00718 sha: doc_id: 300379 cord_uid: db79kb5c file: cache/cord-283405-aozxvxxs.json key: cord-283405-aozxvxxs authors: Vermillion, Meghan S.; 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Zhu, Anjing; Ren, Kai; Li, Shilin; Chen, Limin title: DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1 date: 2020-10-17 journal: Life Sci DOI: 10.1016/j.lfs.2020.118564 sha: doc_id: 309275 cord_uid: soffxxqu file: cache/cord-311007-0i1abjfa.json key: cord-311007-0i1abjfa authors: Schwarz, Megan C.; Sourisseau, Marion; Espino, Michael M.; Gray, Essanna S.; Chambers, Matthew T.; Tortorella, Domenico; Evans, Matthew J. title: Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone date: 2016-09-28 journal: mSphere DOI: 10.1128/msphere.00246-16 sha: doc_id: 311007 cord_uid: 0i1abjfa file: cache/cord-295351-0zr2e8lh.json key: cord-295351-0zr2e8lh authors: Mohd Ropidi, Muhammad Izzuddin; Khazali, Ahmad Suhail; Nor Rashid, Nurshamimi; Yusof, Rohana title: Endoplasmic reticulum: a focal point of Zika virus infection date: 2020-01-20 journal: J Biomed Sci DOI: 10.1186/s12929-020-0618-6 sha: doc_id: 295351 cord_uid: 0zr2e8lh file: cache/cord-290385-0smnl70i.json key: cord-290385-0smnl70i authors: Chan, Jasper F.W.; Choi, Garnet K.Y.; Yip, Cyril C.Y.; Cheng, Vincent C.C.; Yuen, Kwok-Yung title: Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease date: 2016-03-03 journal: J Infect DOI: 10.1016/j.jinf.2016.02.011 sha: doc_id: 290385 cord_uid: 0smnl70i file: cache/cord-294798-ji3p0l4j.json key: cord-294798-ji3p0l4j authors: White, Sarah K.; Mavian, Carla; Elbadry, Maha A.; Beau De Rochars, Valery Madsen; Paisie, Taylor; Telisma, Taina; Salemi, Marco; Lednicky, John A.; Morris, J. Glenn title: Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014 date: 2018-05-31 journal: PLoS Negl Trop Dis DOI: 10.1371/journal.pntd.0006505 sha: doc_id: 294798 cord_uid: ji3p0l4j file: cache/cord-354546-lgkqwm6u.json key: cord-354546-lgkqwm6u authors: Yin, Yingxian; Xu, Yi; Su, Ling; Zhu, Xun; Chen, Minxia; Zhu, Weijin; Xia, Huimin; Huang, Xi; Gong, Sitang title: Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission date: 2016-09-07 journal: Emerg Microbes Infect DOI: 10.1038/emi.2016.100 sha: doc_id: 354546 cord_uid: lgkqwm6u file: cache/cord-015352-2d02eq3y.json key: cord-015352-2d02eq3y authors: nan title: ESPR 2017 date: 2017-04-26 journal: Pediatr Radiol DOI: 10.1007/s00247-017-3820-2 sha: doc_id: 15352 cord_uid: 2d02eq3y file: cache/cord-345238-p841weif.json key: cord-345238-p841weif authors: Magalhaes, Tereza; Chalegre, Karlos Diogo M.; Braga, Cynthia; Foy, Brian D. title: The Endless Challenges of Arboviral Diseases in Brazil date: 2020-05-09 journal: Trop Med Infect Dis DOI: 10.3390/tropicalmed5020075 sha: doc_id: 345238 cord_uid: p841weif file: cache/cord-326512-iex98lr1.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: No child processes key: cord-326512-iex98lr1 authors: Niu, Xuefeng; Zhao, Lingzhai; Qu, Linbing; Yao, Zhipeng; Zhang, Fan; Yan, Qihong; Zhang, Shengnan; Liang, Renshan; Chen, Peihai; Luo, Jia; Xu, Wei; Lv, Huibin; Liu, Xinglong; Lei, Hui; Yi, Changhua; Li, Pingchao; Wang, Qian; Wang, Yang; Yu, Lei; Zhang, Xiaoyan; Bryan, L. Aubrey; Davidson, Edgar; Doranz, j. Benjamin; Feng, Liqiang; Pan, Weiqi; Zhang, Fuchun; Chen, Ling title: Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model date: 2019-05-25 journal: Emerg Microbes Infect DOI: 10.1080/22221751.2019.1614885 sha: doc_id: 326512 cord_uid: iex98lr1 file: cache/cord-340907-j9i1wlak.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: No child processes key: cord-340907-j9i1wlak authors: Zarai, Yoram; Zafrir, Zohar; Siridechadilok, Bunpote; Suphatrakul, Amporn; Roopin, Modi; Julander, Justin; Tuller, Tamir title: Evolutionary selection against short nucleotide sequences in viruses and their related hosts date: 2020-04-27 journal: DNA Res DOI: 10.1093/dnares/dsaa008 sha: doc_id: 340907 cord_uid: j9i1wlak file: cache/cord-341907-vql8e2j3.json /data-disk/reader-compute/reader-cord/bin/json2txt-carrel.sh: fork: retry: No child processes key: cord-341907-vql8e2j3 authors: Wang, Xinyi; Tai, Wanbo; Zhang, Xiaolu; Zhou, Yusen; Du, Lanying; Shen, Chuanlai title: Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine date: 2019-10-27 journal: Vaccines (Basel) DOI: 10.3390/vaccines7040161 sha: doc_id: 341907 cord_uid: vql8e2j3 file: cache/cord-010119-t1x9gknd.json key: cord-010119-t1x9gknd authors: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 journal: Transfusion DOI: 10.1111/trf.14286 sha: doc_id: 10119 cord_uid: t1x9gknd Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-zikv-cord parallel: Warning: Only enough available processes to run 23 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Only enough available processes to run 8 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Only enough available processes to run 27 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Only enough available processes to run 14 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. parallel: Warning: Only enough available processes to run 10 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-002247-e0z5ypii author: Squires, Raynal C title: Preparedness for Zika virus testing in the World Health Organization Western Pacific Region date: 2016-03-31 pages: extension: .txt txt: ./txt/cord-002247-e0z5ypii.txt cache: ./cache/cord-002247-e0z5ypii.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002247-e0z5ypii.txt' === file2bib.sh === id: cord-002754-xlk4xpv2 author: Mögling, Ramona title: Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016 date: 2017-09-07 pages: extension: .txt txt: ./txt/cord-002754-xlk4xpv2.txt cache: ./cache/cord-002754-xlk4xpv2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002754-xlk4xpv2.txt' === file2bib.sh === id: cord-003453-p2buyrcj author: Batista, Mariana N. title: Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date: 2019-01-11 pages: extension: .txt txt: ./txt/cord-003453-p2buyrcj.txt cache: ./cache/cord-003453-p2buyrcj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003453-p2buyrcj.txt' === file2bib.sh === id: cord-004418-08dljap3 author: Young, Ginger title: Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date: 2020-02-26 pages: extension: .txt txt: ./txt/cord-004418-08dljap3.txt cache: ./cache/cord-004418-08dljap3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004418-08dljap3.txt' === file2bib.sh === id: cord-002720-lrkscs71 author: Kurosaki, Yohei title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date: 2017-10-18 pages: extension: .txt txt: ./txt/cord-002720-lrkscs71.txt cache: ./cache/cord-002720-lrkscs71.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002720-lrkscs71.txt' === file2bib.sh === id: cord-003403-ypefqm71 author: Roberts, Christine C. title: Assay Challenges for Emerging Infectious Diseases: The Zika Experience date: 2018-10-02 pages: extension: .txt txt: ./txt/cord-003403-ypefqm71.txt cache: ./cache/cord-003403-ypefqm71.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003403-ypefqm71.txt' === file2bib.sh === id: cord-009399-6zpkpdzu author: Sun, Fang title: Topology, Antiviral Functional Residues and Mechanism of IFITM1 date: 2020-03-08 pages: extension: .txt txt: ./txt/cord-009399-6zpkpdzu.txt cache: ./cache/cord-009399-6zpkpdzu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009399-6zpkpdzu.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-002164-oqc9h2lu author: Kumar, Ashutosh title: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome date: 2016-08-09 pages: extension: .txt txt: ./txt/cord-002164-oqc9h2lu.txt cache: ./cache/cord-002164-oqc9h2lu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-002164-oqc9h2lu.txt' === file2bib.sh === id: cord-002581-r7mskri0 author: Magnani, Diogo M. title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus date: 2017-06-12 pages: extension: .txt txt: ./txt/cord-002581-r7mskri0.txt cache: ./cache/cord-002581-r7mskri0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002581-r7mskri0.txt' === file2bib.sh === id: cord-002341-v4r5d26a author: Chan, Jasper Fuk-Woo title: Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons date: 2016-11-12 pages: extension: .txt txt: ./txt/cord-002341-v4r5d26a.txt cache: ./cache/cord-002341-v4r5d26a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002341-v4r5d26a.txt' === file2bib.sh === id: cord-003187-qdbcdn2j author: Bassi, Maria Rosaria title: Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs date: 2018-08-27 pages: extension: .txt txt: ./txt/cord-003187-qdbcdn2j.txt cache: ./cache/cord-003187-qdbcdn2j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003187-qdbcdn2j.txt' === file2bib.sh === id: cord-003482-f1uvohf0 author: Malmlov, Ashley title: Experimental Zika virus infection of Jamaican fruit bats (Artibeus jamaicensis) and possible entry of virus into brain via activated microglial cells date: 2019-02-04 pages: extension: .txt txt: ./txt/cord-003482-f1uvohf0.txt cache: ./cache/cord-003482-f1uvohf0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003482-f1uvohf0.txt' === file2bib.sh === id: cord-003041-v9uevz3l author: Zukor, Katherine title: Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice date: 2018-02-23 pages: extension: .txt txt: ./txt/cord-003041-v9uevz3l.txt cache: ./cache/cord-003041-v9uevz3l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003041-v9uevz3l.txt' === file2bib.sh === id: cord-003284-hjx2d5rq author: Márquez-Jurado, Silvia title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date: 2018-10-07 pages: extension: .txt txt: ./txt/cord-003284-hjx2d5rq.txt cache: ./cache/cord-003284-hjx2d5rq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003284-hjx2d5rq.txt' === file2bib.sh === id: cord-004053-nmt221tu author: Goh, Gerard Kian-Meng title: Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity date: 2019-11-06 pages: extension: .txt txt: ./txt/cord-004053-nmt221tu.txt cache: ./cache/cord-004053-nmt221tu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-004053-nmt221tu.txt' === file2bib.sh === id: cord-102796-rr8qet8c author: Counotte, Michel J title: Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak date: 2020-03-18 pages: extension: .txt txt: ./txt/cord-102796-rr8qet8c.txt cache: ./cache/cord-102796-rr8qet8c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102796-rr8qet8c.txt' === file2bib.sh === id: cord-102612-xx5l8r9e author: Kodani, Andrew title: Zika virus alters centrosome organization to suppress the innate immune response date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-102612-xx5l8r9e.txt cache: ./cache/cord-102612-xx5l8r9e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102612-xx5l8r9e.txt' === file2bib.sh === id: cord-004022-cr0zskcw author: Lu, Chien-Yi title: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date: 2019-10-31 pages: extension: .txt txt: ./txt/cord-004022-cr0zskcw.txt cache: ./cache/cord-004022-cr0zskcw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-004022-cr0zskcw.txt' === file2bib.sh === id: cord-102279-ena1usqv author: Long, Rory K. M. title: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-102279-ena1usqv.txt cache: ./cache/cord-102279-ena1usqv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102279-ena1usqv.txt' === file2bib.sh === id: cord-004020-qtwcbn7m author: Gao, Yaning title: Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date: 2019-11-02 pages: extension: .txt txt: ./txt/cord-004020-qtwcbn7m.txt cache: ./cache/cord-004020-qtwcbn7m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004020-qtwcbn7m.txt' === file2bib.sh === id: cord-016796-g4kqqpy1 author: Bramhachari, Pallaval Veera title: Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges date: 2019-11-05 pages: extension: .txt txt: ./txt/cord-016796-g4kqqpy1.txt cache: ./cache/cord-016796-g4kqqpy1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016796-g4kqqpy1.txt' === file2bib.sh === id: cord-260336-kwzo8puo author: Si, Lulu title: A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue date: 2019-09-27 pages: extension: .txt txt: ./txt/cord-260336-kwzo8puo.txt cache: ./cache/cord-260336-kwzo8puo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260336-kwzo8puo.txt' === file2bib.sh === id: cord-284646-fhruiw23 author: Jaeger, Anna S. title: Spondweni virus causes fetal harm in Ifnar1(-/-) mice and is transmitted by Aedes aegypti mosquitoes date: 2020-05-24 pages: extension: .txt txt: ./txt/cord-284646-fhruiw23.txt cache: ./cache/cord-284646-fhruiw23.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284646-fhruiw23.txt' === file2bib.sh === id: cord-257539-01s21vh0 author: Delvecchio, Rodrigo title: Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models date: 2016-11-29 pages: extension: .txt txt: ./txt/cord-257539-01s21vh0.txt cache: ./cache/cord-257539-01s21vh0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-257539-01s21vh0.txt' === file2bib.sh === id: cord-253616-7jyui5ca author: Lai, Zheng-Zong title: Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms date: 2020-09-07 pages: extension: .txt txt: ./txt/cord-253616-7jyui5ca.txt cache: ./cache/cord-253616-7jyui5ca.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-253616-7jyui5ca.txt' === file2bib.sh === id: cord-272405-jmwn8pdn author: Parvez, Mohammad K. title: Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future date: 2017-08-04 pages: extension: .txt txt: ./txt/cord-272405-jmwn8pdn.txt cache: ./cache/cord-272405-jmwn8pdn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-272405-jmwn8pdn.txt' === file2bib.sh === id: cord-263868-ewnf96cz author: Srivastava, Mayank title: Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-263868-ewnf96cz.txt cache: ./cache/cord-263868-ewnf96cz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263868-ewnf96cz.txt' === file2bib.sh === id: cord-278286-1xk31726 author: Mutso, Margit title: Basic insights into Zika virus infection of neuroglial and brain endothelial cells date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-278286-1xk31726.txt cache: ./cache/cord-278286-1xk31726.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-278286-1xk31726.txt' === file2bib.sh === id: cord-273065-peqz7okh author: Girard, Marc title: Arboviruses: A global public health threat date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-273065-peqz7okh.txt cache: ./cache/cord-273065-peqz7okh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273065-peqz7okh.txt' === file2bib.sh === id: cord-321312-hgp2jwbl author: Carvalho, Sandhra M. title: Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-321312-hgp2jwbl.txt cache: ./cache/cord-321312-hgp2jwbl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-321312-hgp2jwbl.txt' === file2bib.sh === id: cord-292830-gcfx1095 author: Ianevski, Aleksandr title: Novel activities of safe-in-human broad-spectrum antiviral agents date: 2018-04-23 pages: extension: .txt txt: ./txt/cord-292830-gcfx1095.txt cache: ./cache/cord-292830-gcfx1095.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-292830-gcfx1095.txt' === file2bib.sh === id: cord-338136-nbtkl5cx author: Clemente, Nuria Sanchez title: Geographies of risk: Emerging infectious diseases and travel health data date: 2020-06-25 pages: extension: .txt txt: ./txt/cord-338136-nbtkl5cx.txt cache: ./cache/cord-338136-nbtkl5cx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-338136-nbtkl5cx.txt' === file2bib.sh === id: cord-300459-tu2xrt9x author: Li, Cui title: A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos date: 2018-05-01 pages: extension: .txt txt: ./txt/cord-300459-tu2xrt9x.txt cache: ./cache/cord-300459-tu2xrt9x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-300459-tu2xrt9x.txt' === file2bib.sh === id: cord-330743-o11d0aa1 author: Yu, Xi title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-330743-o11d0aa1.txt cache: ./cache/cord-330743-o11d0aa1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330743-o11d0aa1.txt' === file2bib.sh === id: cord-298166-045evk7g author: Röcker, Annika E. title: The molecular tweezer CLR01 inhibits Ebola and Zika virus infection date: 2018-02-08 pages: extension: .txt txt: ./txt/cord-298166-045evk7g.txt cache: ./cache/cord-298166-045evk7g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-298166-045evk7g.txt' === file2bib.sh === id: cord-332473-ec8lu2a3 author: Amorim, Raquel title: Zika virus inhibits eIF2α-dependent stress granule assembly date: 2017-07-17 pages: extension: .txt txt: ./txt/cord-332473-ec8lu2a3.txt cache: ./cache/cord-332473-ec8lu2a3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332473-ec8lu2a3.txt' === file2bib.sh === id: cord-273326-gmw8gl2r author: Saiz, Juan-Carlos title: Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date: 2018-08-24 pages: extension: .txt txt: ./txt/cord-273326-gmw8gl2r.txt cache: ./cache/cord-273326-gmw8gl2r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273326-gmw8gl2r.txt' === file2bib.sh === id: cord-300379-db79kb5c author: Park, Jun-Gyu title: Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid date: 2019-04-12 pages: extension: .txt txt: ./txt/cord-300379-db79kb5c.txt cache: ./cache/cord-300379-db79kb5c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-300379-db79kb5c.txt' === file2bib.sh === id: cord-262944-9k64f0tw author: Parker, Elaine L. title: Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-262944-9k64f0tw.txt cache: ./cache/cord-262944-9k64f0tw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-262944-9k64f0tw.txt' === file2bib.sh === id: cord-319781-6thdg2up author: Payne, Kelly title: Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-319781-6thdg2up.txt cache: ./cache/cord-319781-6thdg2up.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-319781-6thdg2up.txt' === file2bib.sh === id: cord-283405-aozxvxxs author: Vermillion, Meghan S. title: Pregnancy and infection: using disease pathogenesis to inform vaccine strategy date: 2018-02-01 pages: extension: .txt txt: ./txt/cord-283405-aozxvxxs.txt cache: ./cache/cord-283405-aozxvxxs.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283405-aozxvxxs.txt' === file2bib.sh === id: cord-309275-soffxxqu author: Li, Shuang title: DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1 date: 2020-10-17 pages: extension: .txt txt: ./txt/cord-309275-soffxxqu.txt cache: ./cache/cord-309275-soffxxqu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-309275-soffxxqu.txt' === file2bib.sh === id: cord-310004-h9ixhhzz author: Yuan, Shuofeng title: Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-310004-h9ixhhzz.txt cache: ./cache/cord-310004-h9ixhhzz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310004-h9ixhhzz.txt' === file2bib.sh === id: cord-345238-p841weif author: Magalhaes, Tereza title: The Endless Challenges of Arboviral Diseases in Brazil date: 2020-05-09 pages: extension: .txt txt: ./txt/cord-345238-p841weif.txt cache: ./cache/cord-345238-p841weif.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-345238-p841weif.txt' === file2bib.sh === id: cord-311007-0i1abjfa author: Schwarz, Megan C. title: Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone date: 2016-09-28 pages: extension: .txt txt: ./txt/cord-311007-0i1abjfa.txt cache: ./cache/cord-311007-0i1abjfa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-311007-0i1abjfa.txt' === file2bib.sh === id: cord-354546-lgkqwm6u author: Yin, Yingxian title: Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission date: 2016-09-07 pages: extension: .txt txt: ./txt/cord-354546-lgkqwm6u.txt cache: ./cache/cord-354546-lgkqwm6u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354546-lgkqwm6u.txt' === file2bib.sh === id: cord-294798-ji3p0l4j author: White, Sarah K. title: Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014 date: 2018-05-31 pages: extension: .txt txt: ./txt/cord-294798-ji3p0l4j.txt cache: ./cache/cord-294798-ji3p0l4j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-294798-ji3p0l4j.txt' === file2bib.sh === id: cord-295351-0zr2e8lh author: Mohd Ropidi, Muhammad Izzuddin title: Endoplasmic reticulum: a focal point of Zika virus infection date: 2020-01-20 pages: extension: .txt txt: ./txt/cord-295351-0zr2e8lh.txt cache: ./cache/cord-295351-0zr2e8lh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-295351-0zr2e8lh.txt' === file2bib.sh === id: cord-326512-iex98lr1 author: Niu, Xuefeng title: Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model date: 2019-05-25 pages: extension: .txt txt: ./txt/cord-326512-iex98lr1.txt cache: ./cache/cord-326512-iex98lr1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326512-iex98lr1.txt' === file2bib.sh === id: cord-290385-0smnl70i author: Chan, Jasper F.W. title: Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease date: 2016-03-03 pages: extension: .txt txt: ./txt/cord-290385-0smnl70i.txt cache: ./cache/cord-290385-0smnl70i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-290385-0smnl70i.txt' === file2bib.sh === id: cord-340907-j9i1wlak author: Zarai, Yoram title: Evolutionary selection against short nucleotide sequences in viruses and their related hosts date: 2020-04-27 pages: extension: .txt txt: ./txt/cord-340907-j9i1wlak.txt cache: ./cache/cord-340907-j9i1wlak.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340907-j9i1wlak.txt' === file2bib.sh === id: cord-341907-vql8e2j3 author: Wang, Xinyi title: Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine date: 2019-10-27 pages: extension: .txt txt: ./txt/cord-341907-vql8e2j3.txt cache: ./cache/cord-341907-vql8e2j3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341907-vql8e2j3.txt' === file2bib.sh === id: cord-015352-2d02eq3y author: nan title: ESPR 2017 date: 2017-04-26 pages: extension: .txt txt: ./txt/cord-015352-2d02eq3y.txt cache: ./cache/cord-015352-2d02eq3y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-015352-2d02eq3y.txt' === file2bib.sh === id: cord-010119-t1x9gknd author: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 pages: extension: .txt txt: ./txt/cord-010119-t1x9gknd.txt cache: ./cache/cord-010119-t1x9gknd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-010119-t1x9gknd.txt' Que is empty; done keyword-zikv-cord === reduce.pl bib === id = cord-002341-v4r5d26a author = Chan, Jasper Fuk-Woo title = Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons date = 2016-11-12 pages = extension = .txt mime = text/plain words = 7155 sentences = 399 flesch = 52 summary = To establish a novel mouse model for ZIKV infection, we compared the clinical, histological, and virological findings of male (group 1) and female (group 2) mice with dexamethasone immunosuppression and ZIKV inoculation with those of the appropriate controls (groups 3 to 8) (Table 1 ). The dexamethasone-immunosuppressed mice with ZIKV inoculation in our study developed disseminated infection with viremia and multi-organ involvement, including the brain, urogenital tract, intestine, liver, spleen, pancreas, heart, lung, and salivary gland as evident by ZIKV-NS1 protein expression on immunohistochemical staining and/or detectable viral load in these tissues. Our findings provided an additional explanation for the pathogenesis of fatal ZIKV infection, which has been proposed to be related to uncontrolled virus dissemination in previously described mouse models utilizing types I/II interferon-signaling-/receptor-deficient mice that were unable to mount a robust host innate immune response. cache = ./cache/cord-002341-v4r5d26a.txt txt = ./txt/cord-002341-v4r5d26a.txt === reduce.pl bib === id = cord-002247-e0z5ypii author = Squires, Raynal C title = Preparedness for Zika virus testing in the World Health Organization Western Pacific Region date = 2016-03-31 pages = extension = .txt mime = text/plain words = 1568 sentences = 78 flesch = 40 summary = On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern. The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection. A total of 28 surveys to national-level laboratories likely to be tasked with ZIKV testing were distributed to 19 countries in the Region (omitting resource-limited countries with Zika virus testing preparedness in the Western Pacific Region Squires & Konings reporting having this capacity. While this survey reveals a broad availability of molecular diagnostics to support surveillance of ZIKV in the Western Pacific Region, further key roles remain for laboratories in helping to unravel the pathogenicity of the virus and its potential causal role in the observed cases of microcephaly and other neurological disorders. cache = ./cache/cord-002247-e0z5ypii.txt txt = ./txt/cord-002247-e0z5ypii.txt === reduce.pl bib === id = cord-002720-lrkscs71 author = Kurosaki, Yohei title = Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date = 2017-10-18 pages = extension = .txt mime = text/plain words = 4950 sentences = 251 flesch = 55 summary = title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. Therefore, it is difficult to detect ZIKV in blood samples from patients after the acute phase of infection, even with sensitive molecular diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR) 14, 18, 19 . These results suggested that the RT-LAMP assay could be used as a rapid, sensitive diagnostic test for ZIKV, the Tp value (i.e., less than 15 min) can be used as an indicator of the number of RNA copies in each reaction. cache = ./cache/cord-002720-lrkscs71.txt txt = ./txt/cord-002720-lrkscs71.txt === reduce.pl bib === id = cord-003187-qdbcdn2j author = Bassi, Maria Rosaria title = Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs date = 2018-08-27 pages = extension = .txt mime = text/plain words = 6701 sentences = 337 flesch = 41 summary = Although the two viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin), while USUV replication is suppressed more efficiently by 5-fluorouracil. We observe that ribavirin, favipiravir, and 5-fluorouracil are all inhibitors of both ZIKV and USUV, and that consecutive passage of virus in the presence of these drugs can lead to the complete extinction of infectivity. To investigate whether ZIKV replication could be affected by increased mutagenesis, we tested four different compounds known to be mutagenic for diverse viruses, 5-fluorouracil, ribavirin, favipiravir, and decitabine (25, 32, 35, (37) (38) (39) . To investigate whether the antiviral activities observed during treatment with favipiravir, ribavirin, and 5-fluorouracil are connected to their predicted mutagenic activity, we analyzed the mutation frequencies of both ZIKV and USUV rescued after 5 passages in the presence of these compounds. cache = ./cache/cord-003187-qdbcdn2j.txt txt = ./txt/cord-003187-qdbcdn2j.txt === reduce.pl bib === id = cord-002581-r7mskri0 author = Magnani, Diogo M. title = A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus date = 2017-06-12 pages = extension = .txt mime = text/plain words = 5291 sentences = 313 flesch = 55 summary = title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the isolation of 18 plasmablast-derived human mAbs, sorted 12 days post onset of symptoms from a ZIKV-patient in São Paulo, Brazil. Interestingly, one of these mAbs (P1F12) exhibited no nucleotide mutations when compared to its corresponding germline sequences, but still recognized a ZIKV immunodominant epitope and neutralized the virus. Virus capture assay and recombinant E protein ELISA P1F12 binding was determined by both virus capture assay (VCA) and recombinant (r)E ELISAs. The VCA plates were coated overnight with the mouse-anti-Flavivirus monoclonal antibody 4G2 (clone D1-4G2-4-15, EMD Millipore) followed by incubation with viral stocks (ZIKV or DENV). Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus cache = ./cache/cord-002581-r7mskri0.txt txt = ./txt/cord-002581-r7mskri0.txt === reduce.pl bib === id = cord-002754-xlk4xpv2 author = Mögling, Ramona title = Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016 date = 2017-09-07 pages = extension = .txt mime = text/plain words = 3936 sentences = 203 flesch = 42 summary = title: Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016 To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. To map ZIKV expertise and identify diagnostic capacity and capability gaps in Europe during the initial phase of the PHEIC in February 2016, the European Commission (EC) asked the European Centre for Disease Prevention and Control (ECDC) for a rapid assessment of the capacity of laboratories in Europe to detect ZIKV infections and the specific needs for support. The availability of validation materials, positive controls and personnel were indicated as the main challenges for implementation of ZIKV diagnostics in the reference laboratories of the 30 EU/EEA countries. cache = ./cache/cord-002754-xlk4xpv2.txt txt = ./txt/cord-002754-xlk4xpv2.txt === reduce.pl bib === id = cord-003041-v9uevz3l author = Zukor, Katherine title = Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice date = 2018-02-23 pages = extension = .txt mime = text/plain words = 8909 sentences = 454 flesch = 51 summary = This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizurelike activity during the acute phase of disease. This study demonstrates that a contemporary strain of ZIKV (PRVABC59) can widely infect astrocytes and neurons in the brain and spinal cord of adult AG129 mice and cause rapidly progressing hindlimb paralysis, as well as severe seizure activity, during the acute phase of disease. cache = ./cache/cord-003041-v9uevz3l.txt txt = ./txt/cord-003041-v9uevz3l.txt === reduce.pl bib === id = cord-003284-hjx2d5rq author = Márquez-Jurado, Silvia title = An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date = 2018-10-07 pages = extension = .txt mime = text/plain words = 9917 sentences = 409 flesch = 51 summary = Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. To analyze the genetic stability of the recombinant ZIKV harboring the point mutation A175V in the coding region of the NS2A protein (rZIKV-RGN-mNS2A), total RNA was purified from Vero cells infected with viruses from passage 1 (P1) to passage 5 (P5) using the RNeasy minikit (Qiagen), according to the manufacturer's specifications. To investigate whether the reduced RNA synthesis of rZIKV-RGN-mNS2A in Vero cells could result in viral attenuation in vivo, the ability of the mutant virus to induce pathogenesis was analyzed in A129 mice and compared with that of the parental rZIKV-RGN ( Figure 6 ). cache = ./cache/cord-003284-hjx2d5rq.txt txt = ./txt/cord-003284-hjx2d5rq.txt === reduce.pl bib === id = cord-003403-ypefqm71 author = Roberts, Christine C. title = Assay Challenges for Emerging Infectious Diseases: The Zika Experience date = 2018-10-02 pages = extension = .txt mime = text/plain words = 4957 sentences = 248 flesch = 42 summary = When initial Zika vaccine clinical trials were being designed and launched in response to the outbreak, there were no standardized sets of viral and immunological assays, and no approved diagnostic tests for Zika virus infection. In an outbreak situation, such as with Zika, it is important to have the ability to quickly develop both diagnostic kits for public health purposes and vaccine clinical assays to support pre-clinical studies and early stage clinical trials. Additionally, cross-reactivity in a number of immunological assays and the short time frame in which viremia can be detected in bodily fluids necessitated the institution of an algorithm to confirm ZIKV infection that was based on a combination of risk factors, clinical symptoms and diagnostic test results [71] . Rapid response to an emerging infectious disease-lessons learned from development of a synthetic DNA vaccine targeting Zika virus cache = ./cache/cord-003403-ypefqm71.txt txt = ./txt/cord-003403-ypefqm71.txt === reduce.pl bib === id = cord-003453-p2buyrcj author = Batista, Mariana N. title = Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date = 2019-01-11 pages = extension = .txt mime = text/plain words = 4157 sentences = 220 flesch = 49 summary = In this study, we tested the activity of the natural compounds berberine and emodin for their ability to inhibit ZIKV infection. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. cache = ./cache/cord-003453-p2buyrcj.txt txt = ./txt/cord-003453-p2buyrcj.txt === reduce.pl bib === id = cord-003482-f1uvohf0 author = Malmlov, Ashley title = Experimental Zika virus infection of Jamaican fruit bats (Artibeus jamaicensis) and possible entry of virus into brain via activated microglial cells date = 2019-02-04 pages = extension = .txt mime = text/plain words = 7503 sentences = 400 flesch = 53 summary = Quantitative probe-based reverse transcription PCR (qRT-PCR) was performed on seruminoculated Vero cell supernatants, serum, brain, lung, liver, spleen, kidney, urinary bladder, prostate and testes from bats from both studies. Brain and testicular tissues stained with both goat polyclonal goat anti-Iba1 (green) and monoclonal 4G-2 flavivirus E specific antibodies (red) showed co-localization (yellow) of ZIKV antigen in cytoplasm of activated microglial cells with their characteristic morphology in the cerebral cortex of infected bats 10 dpi in the time course study and 28 day dpi in the pilot study (Fig 9) . Two bat infection experiments were conducted in this investigation; 1) a pilot study to determine susceptibility of Jamaican fruit bats to ZIKV infection, and 2) a time course study to better understand pathophysiology and chronology of events pertaining to the dynamics of viremia, viral tropism, replication and shedding of the virus in a New World bat species. cache = ./cache/cord-003482-f1uvohf0.txt txt = ./txt/cord-003482-f1uvohf0.txt === reduce.pl bib === id = cord-004418-08dljap3 author = Young, Ginger title = Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date = 2020-02-26 pages = extension = .txt mime = text/plain words = 4619 sentences = 265 flesch = 53 summary = In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. As with neutralizing antibodies, all PIZV doses were immunogenic and no anti-Zika IgG was detected in the control group prior to ZIKV challenge. PIZV elicited a dose dependent neutralizing antibody immune response and an anti-Zika IgG response which correlated with a reduction in ZIKV vRNA post-challenge (Table 2 ). Vaccinating with a broad range of PIZV dose levels enabled us to correlate both neutralizing and anti-Zika IgG antibody titers to protection against ZIKV infection. A Zika RVP assay (Sonnberg et al., manuscript in preparation) was used to determine neutralizing antibody titers in serum following the administration of PIZV (study days 1, 29, 57, and 71), and 30 days post-ZIKV challenge (day 101). cache = ./cache/cord-004418-08dljap3.txt txt = ./txt/cord-004418-08dljap3.txt === reduce.pl bib === id = cord-009399-6zpkpdzu author = Sun, Fang title = Topology, Antiviral Functional Residues and Mechanism of IFITM1 date = 2020-03-08 pages = extension = .txt mime = text/plain words = 5697 sentences = 354 flesch = 57 summary = Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Some studies suggest that IFITM proteins may suppress the entry of viruses by inhibiting the hemifusion of viral membrane and host cell membranes [15] or restricting the formation of fusion pores following virus-endosome hemifusion [16] . Alanine scanning and site-directed mutations found that KRRK basic residues were key for the restriction of IFITM proteins on ZIKV and DENV. Significantly, we found that IFITM1 can restrict the release of ZIKV from endosome to cytosol to prevent the entry of viral particles into host cells, which was associated with its inhibition on organelles acidification. cache = ./cache/cord-009399-6zpkpdzu.txt txt = ./txt/cord-009399-6zpkpdzu.txt === reduce.pl bib === id = cord-002164-oqc9h2lu author = Kumar, Ashutosh title = A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome date = 2016-08-09 pages = extension = .txt mime = text/plain words = 5809 sentences = 256 flesch = 40 summary = We, for this important reason, searched for the RARE consensus sequence (5 ′ -AGGTCA-3 ′ ) repeats in the genomic sequences of the ZIKV strains with a hypothesis that the virus might act through disruption of normal retinoic acid signaling mediated by incorporation of these sequences into the DNA of developing host brain cells. In view of (1) the bioinformatic evidence of the presence of RARE sequence repeats in genome sequences of ZIKV strains and in other viruses known to cause congenital brain malformation (Table 3) and (2) confirmed role of retinoic acid in neural tube formation and further brain development mediated through RARE sequences, it is scientifically coherent to assume that a RARE sequence dependent mechanism could be the underlying mechanism of microcephaly seen in ZIKV infected fetuses. cache = ./cache/cord-002164-oqc9h2lu.txt txt = ./txt/cord-002164-oqc9h2lu.txt === reduce.pl bib === id = cord-004053-nmt221tu author = Goh, Gerard Kian-Meng title = Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity date = 2019-11-06 pages = extension = .txt mime = text/plain words = 6456 sentences = 326 flesch = 60 summary = Percentages of intrinsic disorder (PIDs) of M and C shell proteins from Zika virus (ZIKV) strains with UniProt accession. According to our research on other viruses, the capsid association with virulence involves a mechanism of protein promiscuity, whereby intrinsic disorder allows the capsid protein (the C protein, in the case of flaviviruses) to bind to a greater number of proteins, thereby allowing the virus to multiply more rapidly before the host immune system can take action [2, 14, 51] . It is therefore likely that the different PIDs of C proteins from the various ZIKV strains and lineages are the result of the types of primates that the peculiar ZIKV strain primarily infects and its ability to fine-tune its C disorder to meet the optimal viral load necessary for more efficient transmission of the virus in a given host, as seen in the case of other viruses and other flaviviruses [2, 14, 25, 39, 49, 50] . cache = ./cache/cord-004053-nmt221tu.txt txt = ./txt/cord-004053-nmt221tu.txt === reduce.pl bib === id = cord-004020-qtwcbn7m author = Gao, Yaning title = Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date = 2019-11-02 pages = extension = .txt mime = text/plain words = 7693 sentences = 354 flesch = 50 summary = A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Gossypol-treated ZIKV was incubated with Vero E6 cells at 37 • C for 1 h in the presence of DMEM containing serial dilutions of each of the other three natural products identified, such as curcumin, digitonin, and conessine, or anti-ZIKV compound control (bortezomib). Based on Table 1 , four "hit" natural products, including gossypol, curcumin, digitonin, and conessine ( Figure 2A -D), were selected, since they demonstrated inhibitory activity against ZIKV infection with no obvious cytotoxicity in Vero E6 cells when observed under a microscope. Since gossypol demonstrated the highest antiviral activity individually against all ZIKV strains tested, we next investigated the potential combinatorial effects of the combination of gossypol with three other natural products identified, namely curcumin, digitonin, and conessine, as well as anti-ZIKV compound control (bortezomib). cache = ./cache/cord-004020-qtwcbn7m.txt txt = ./txt/cord-004020-qtwcbn7m.txt === reduce.pl bib === id = cord-004022-cr0zskcw author = Lu, Chien-Yi title = The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date = 2019-10-31 pages = extension = .txt mime = text/plain words = 5532 sentences = 235 flesch = 48 summary = The packaging cells carrying the recombinant plasmid encoding the viral structural proteins are transfected with DNA-launched replicons and then self-replicate viral subgenomes and express all viral proteins, allowing viral assembly and release as SRIPs. Several flavivirus, replicon-based SRIPs, including JEV, dengue virus, West Nile virus, and tick-borne encephalitis virus have been generated and demonstrated as safer vaccine candidates [15] [16] [17] . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . cache = ./cache/cord-004022-cr0zskcw.txt txt = ./txt/cord-004022-cr0zskcw.txt === reduce.pl bib === id = cord-102612-xx5l8r9e author = Kodani, Andrew title = Zika virus alters centrosome organization to suppress the innate immune response date = 2020-09-15 pages = extension = .txt mime = text/plain words = 4895 sentences = 302 flesch = 46 summary = ZIKV infection or loss of CEP63 decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection or loss of CEP63 also increased the centrosomal accumulation of the CEP63 interactors, Mindbomb1 (MIB1) and DTX4, ubiquitin ligases that respectively activate and degrade TBK1. In addition to identifying a mechanism by which CEP63 controls the innate immune responses in ZIKV infection, we propose that the altered centrosomal organization caused by altered CEP63 function may contribute to ZIKV-associated microcephaly. ZIKV infection in U87 cells did not affect either the localization or levels of the MCPH-associated proteins PLK4, STIL, SAS6, CDK5RAP2, CEP152, or WDR62 (Supplemental Figure 2A-D) . In summary, we have found that ZIKV NS3 localizes to the centrosome, recruits CEP63 and its binding partners MIB1 and DTX4 to ubiquitylate and degrade TBK1, a key regulator of the innate immune response. cache = ./cache/cord-102612-xx5l8r9e.txt txt = ./txt/cord-102612-xx5l8r9e.txt === reduce.pl bib === id = cord-016796-g4kqqpy1 author = Bramhachari, Pallaval Veera title = Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges date = 2019-11-05 pages = extension = .txt mime = text/plain words = 5646 sentences = 305 flesch = 34 summary = As a part of modern research on immunotechniques, a diagnostic approach for chronic hepatitis C infection (CHC), detects specific antibody to HCV (anti-HCV) (indirect tests) and assays that can detect, quantify, or characterize components of HCV viral particles, viz. Nonetheless, recent studies on respiratory syncytial virus (RSV) developed Luciferase Immunoprecipitation Systems (LIPS) assay to detect IgG Antibodies against Human RSV G-Glycoprotein. Sensitive and specific detection of Crimean-Congo hemorrhagic fever virus (CCHFV) was developed employing specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests (Emmerich et al. A rapid diagnostic platform for colorimetric differential detection of DENV and CHIKV viral infections was recently developed with a possibility to alter clinical diagnosis of acute febrile illnesses in resource-limited settings. This novel antibody demonstrates noteworthy specificity to identify H7N9 virus compared to homemade target-captured ELISA, qRT-PCR, and rapid influenza diagnostic test (RIDT) with high sensitivity (Chang et al. cache = ./cache/cord-016796-g4kqqpy1.txt txt = ./txt/cord-016796-g4kqqpy1.txt === reduce.pl bib === id = cord-102796-rr8qet8c author = Counotte, Michel J title = Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak date = 2020-03-18 pages = extension = .txt mime = text/plain words = 3046 sentences = 198 flesch = 56 summary = We are continuously facing new disease outbreaks, including the new coronavirus (SARS-nCoV-2) in December 2019.The objective of this study was to describe the accumulation of evidence during the 2013-2016 Zika virus (ZIKV) outbreak in the Pacific and the Americas related to aetiological causal questions about congenital abnormalities and Guillain-Barre syndrome. In the 2013-2016 ZIKV outbreak, case reports, case series and basic research studies were published first. A strength of this study is the pre-specified hypothesis about the time to publication of aetiological 139 research and the use of data from systematic reviews that had screened and selected studies that 140 addressed the causal relationship between ZIKV infection and its adverse outcomes. The accumulation of evidence over time in new causal problems seems to follow a hierarchy where 225 case reports and case series were rapidly followed by basic research. Syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study cache = ./cache/cord-102796-rr8qet8c.txt txt = ./txt/cord-102796-rr8qet8c.txt === reduce.pl bib === id = cord-260336-kwzo8puo author = Si, Lulu title = A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue date = 2019-09-27 pages = extension = .txt mime = text/plain words = 6353 sentences = 337 flesch = 59 summary = Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Student's unpaired two-tailed t-test was used to monitor the distribution of Z2 in male A129 mouse body and testicular tissue and to analyze the difference of viral RNA level in sera or tissues between Z2-and vehicle-treated A129 mice. ZIKV RNA copies in (A) testes, (B) epididymides, and (C) sperm of Z2-or vehicle-treated ZIKV-infected male A129 mice at day 16 were detected by qRT-PCR. Zika virus infection in the testicular tissue not only damages male testicular tissue, resulting in pathological lesion of testes and epididymides, but also produces ZIKV-infected semen, causing infertility. cache = ./cache/cord-260336-kwzo8puo.txt txt = ./txt/cord-260336-kwzo8puo.txt === reduce.pl bib === id = cord-102279-ena1usqv author = Long, Rory K. M. title = Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date = 2020-06-23 pages = extension = .txt mime = text/plain words = 3681 sentences = 275 flesch = 55 summary = projections of 3D STED image stacks show high intensity ERmoxGFP and Sec61β-GFP labeling in a 89 CER region and low intensity labeling in PER tubules in mock-infected cells ( Figure 1A ), as reported 90 previously by diffraction limited confocal microscopy (3). Density-based segmentation of the ERmoxGFP-96 and Sec61β-GFP-labelled ER of ZIKV-infected cells showed that the higher density crescent-shaped 97 CER region exhibited significant overlap with dsRNA-positive ER structures relative to the rest of 98 the ER ( Figure 1B ). Morphological comparison of the dsRNA-positive and -negative CER of 133 ZIKV-infected cells with the CER of mock-infected cells showed that the CER was composed of a 134 convoluted network of tubules for both the ERmoxGFP-and Sec61β-labeled ER ( Figure 3B ). 3D STED analysis showed a predominant distribution of both NS2B and 149 NS4B to the CER and more particularly to the dense ZIKV-induced crescent-shaped tubular matrix 150 in ERmoxGFP transfected U87 cells ( Figure 5A ). cache = ./cache/cord-102279-ena1usqv.txt txt = ./txt/cord-102279-ena1usqv.txt === reduce.pl bib === id = cord-263868-ewnf96cz author = Srivastava, Mayank title = Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor date = 2020-08-04 pages = extension = .txt mime = text/plain words = 7614 sentences = 429 flesch = 52 summary = ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We used the labeled ZIKV to infect Vero cells and interacting proteins were crosslinked at fixed time points to identify the virus-host factors and elucidate the virus entry mechanism (Fig. 1c) . To further investigate whether the strategy was also capable of correlating spatial information with the virus crosslinked proteins, we performed the STRING analysis to determine whether there is statistical overrepresentation of specific genes or proteins in the sample at specific time points and identify proteins specific at the attachment or cellular entry stages ( Supplementary Fig. 6 ). cache = ./cache/cord-263868-ewnf96cz.txt txt = ./txt/cord-263868-ewnf96cz.txt === reduce.pl bib === id = cord-257539-01s21vh0 author = Delvecchio, Rodrigo title = Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models date = 2016-11-29 pages = extension = .txt mime = text/plain words = 5669 sentences = 290 flesch = 52 summary = Immunofluorescence staining corroborated these results ( Figure 1B ) and additionally, chloroquine decreased the production of infectious ( Figure 1C ) and total ( Figure 1D ) virus particles, including defective viral particles, by ZIKV-infected cells. Incubation of Vero cells with chloroquine at 0 h postinfection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. Incubation of Vero cells with chloroquine at 0 h post-infection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). cache = ./cache/cord-257539-01s21vh0.txt txt = ./txt/cord-257539-01s21vh0.txt === reduce.pl bib === id = cord-253616-7jyui5ca author = Lai, Zheng-Zong title = Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms date = 2020-09-07 pages = extension = .txt mime = text/plain words = 4969 sentences = 286 flesch = 48 summary = To investigate the anti-ZIKV activity of harringtonine, we assessed the inhibition of virus infection in Vero cells with MOI = 0.01 under different concentrations of harringtonine for 48 h. Intracellular viral RNA levels, protein expression levels and virus progeny in supernatants were respectively determined by RT-qPCR, western blotting and fluorescent focus assay (FFA). The dose-dependent anti-ZIKV activities of harringtonine were observed to decrease viral RNA/protein production and progeny yield ( Figure 1B-D) , indicating that virus propagation was suppressed. Harringtonine (625 nM) was administered at different stages of ZIKV infection with MOI = 0.1, and then the levels of ZIKV RNA in cells, as well as virus titers in supernatants, were determined after 24 h treatment. Harringtonine (625 nM) was administered at different stages of ZIKV infection with MOI = 0.1, and then the levels of ZIKV RNA in cells, as well as virus titers in supernatants, were determined after 24 h treatment. cache = ./cache/cord-253616-7jyui5ca.txt txt = ./txt/cord-253616-7jyui5ca.txt === reduce.pl bib === id = cord-284646-fhruiw23 author = Jaeger, Anna S. title = Spondweni virus causes fetal harm in Ifnar1(-/-) mice and is transmitted by Aedes aegypti mosquitoes date = 2020-05-24 pages = extension = .txt mime = text/plain words = 3948 sentences = 247 flesch = 57 summary = Vector competence experiments showed that Ae. aegypti could transmit SPONV when 70 exposed to bloodmeal titers that approximate physiological titers, while Cx. quinquefasciatus nonpregnant, mixed sex 6-to 11-week-old mice lacking type I interferon signaling (Ifnar1 -/-) Ar94 (this is the only strain used in these studies, so it will be referred to hereafter as 86 SPONV); or 10 2 PFU of the highly pathogenic African-lineage ZIKV strain DAK AR 41524 87 (ZIKV-DAK) (Jaeger et al., 2019) . Despite significantly higher maternal 141 viremia observed at 4 dpi with ZIKV-DAK-infected dams, the fact that resorption rates did 142 not significantly differ between the two groups indicates that both ZIKV-DAK and SPONV 143 have a propensity to harm the developing fetus that is independent of the amount of 144 replication in maternal blood. In contrast, ZIKV-DAK-and SPONV-inoculated dams displayed 221 varying degrees of placental pathology with severe effects predominantly observed in the 222 the labyrinth zone, including vascular injury involving maternal and/or fetal vascular spaces, 223 infarction (obstructed blood flow), necrosis, apoptosis, and hemorrhage (Fig. 4) . cache = ./cache/cord-284646-fhruiw23.txt txt = ./txt/cord-284646-fhruiw23.txt === reduce.pl bib === id = cord-272405-jmwn8pdn author = Parvez, Mohammad K. title = Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future date = 2017-08-04 pages = extension = .txt mime = text/plain words = 4192 sentences = 210 flesch = 43 summary = Despite substantial advancements in the understanding of the biology of pathogens, the breakthroughs in prevention, and their effects on public health and the global economy, the emergence of novel pandemic viruses remains an enduring puzzle. This review presents an update on the knowledge of important emerging/re-emerging viral infections worldwide, discussing their possible origin, evolution, natural reservoirs, human adaptations, and risk factors ( Fig. 1 ). To understand this further, a recently isolated HEV genotype 3 from a chronic hepatitis E patient containing a recombinant virus-host RNA genome was shown to infect cultured human, pig, and deer hepatocytes [39] . The field of phylodynamics, combining a modeling framework for host, epidemiological, and molecular data, especially for RNA viruses, shows particular promise for Parvez understanding the patterns of viral evolution during epidemics [40, 41] . Despite landmark advances in understanding the nature and biology of many pathogenic viruses, there is limited knowledge on emerging novel viruses, their potential reservoirs, and their modes of transmission. cache = ./cache/cord-272405-jmwn8pdn.txt txt = ./txt/cord-272405-jmwn8pdn.txt === reduce.pl bib === id = cord-278286-1xk31726 author = Mutso, Margit title = Basic insights into Zika virus infection of neuroglial and brain endothelial cells date = 2020-04-30 pages = extension = .txt mime = text/plain words = 6010 sentences = 324 flesch = 54 summary = This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). To characterize infection by different ZIKV strains (MR766, PRVABC59 and BeH819015), brain endothelial cells (hCMEC/D3) and neuroglial olfactory ensheathing cells (hOEC and mOEC) were infected at an m.o.i. of 0.1. To examine the virus persistence in neuroglia and human brain endothelial cell cultures, the viral RNA copy numbers in hCMEC/D3, hOEC and mOEC cells infected with MR766, PRVABC59 and BeH819015 for 2 months were quantified using RT-qPCR (Fig. 6) . cache = ./cache/cord-278286-1xk31726.txt txt = ./txt/cord-278286-1xk31726.txt === reduce.pl bib === id = cord-273065-peqz7okh author = Girard, Marc title = Arboviruses: A global public health threat date = 2020-04-24 pages = extension = .txt mime = text/plain words = 5574 sentences = 241 flesch = 48 summary = The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs. The recent outbreak of neurological disorders and neonatal malformations associated with Zika virus (ZIKV) infection in Latin America {5}, the yellow fever (YFV) epidemics in Angola and Brazil with importation to China [6] , the ever-expanding West Nile virus (WNV) epidemic in the Americas [7] , the recent emergence in East Africa and global spread of chikungunya virus (CHIKV) [8] , as well as the ongoing and expanding dengue virus (DENV) pandemic in the tropics and subtropics [9] have reinforced the call for action in the fight against emerging and re-emerging arboviral diseases. The vaccine showed high efficacy and good safety in seropositive persons in the 9-45 years age group, but a risk of severe dengue was observed in individuals who were naive for DENV infection at the time they were vaccinated. cache = ./cache/cord-273065-peqz7okh.txt txt = ./txt/cord-273065-peqz7okh.txt === reduce.pl bib === id = cord-292830-gcfx1095 author = Ianevski, Aleksandr title = Novel activities of safe-in-human broad-spectrum antiviral agents date = 2018-04-23 pages = extension = .txt mime = text/plain words = 5511 sentences = 298 flesch = 45 summary = Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. Here, we hypothesised that some of the identified safe-in-human BSAs could possess novel antiviral activities and, therefore, could be used for treatment of many different viral infections. Fig. 1 shows BSAs and other approved antiviral drugs linked to viral and host targets through viruses they inhibit. Thus, we tested several known BSA agents against (−)ssRNA, (+) ssRNA, ssRNA-RT and dsDNA viruses and identified novel activities for dalbavancin against EV1, ezetimibe against ZIKV and HIV-1, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against RVFV. We identified novel antiviral activities for dalbavancin (against EV1), ezetimibe (against HIV-1 and ZIKV), azacitidine, cyclosporine, minocycline, oritavancin and ritonavir (against RVFV) (Fig. 4) . cache = ./cache/cord-292830-gcfx1095.txt txt = ./txt/cord-292830-gcfx1095.txt === reduce.pl bib === id = cord-300459-tu2xrt9x author = Li, Cui title = A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos date = 2018-05-01 pages = extension = .txt mime = text/plain words = 6832 sentences = 353 flesch = 56 summary = We previously reported on a panel of monoclonal antibodies (mAbs) derived from the longitudinal samples of a ZIKV-convalescent individual and characterized their neutralizing activities, epitope specificities, and development timeline over the course of infection . Here, we use the mouse models of ZIKV infection and microcephaly to analyze the in vivo protective activities of six human mAbs and compare the findings with our reported in vitro neutralization activity, as measured by plaque reduction neutralization test (PRNT). mAbs that target DIII with potent neutralizing activity have also been isolated by other groups, derived from either infected humans or mice, and have been shown to be effective in various models of ZIKV pathogenesis (Fernandez et al., 2017; Magnani et al., 2017; Robbiani et al., 2017; Stettler et al., 2016; Wang et al., 2017b; Zhao et al., 2016) . cache = ./cache/cord-300459-tu2xrt9x.txt txt = ./txt/cord-300459-tu2xrt9x.txt === reduce.pl bib === id = cord-273326-gmw8gl2r author = Saiz, Juan-Carlos title = Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date = 2018-08-24 pages = extension = .txt mime = text/plain words = 7111 sentences = 293 flesch = 34 summary = In this line, and contrary to above mentioned report [73] , CQ, an FDA-approved anti-inflammatory 4-aminoquinoline and an autophagy inhibitor widely used as an anti-malaria drug that is administered to pregnant women at risk of exposure to Plasmodium parasites, was shown to have anti-ZIKV activity in different cell types (Vero cells, human brain microvascular endothelial cells (hBMECs), and human neural stem cells (NSCs)), affecting early stages of the viral life cycle, possibly by raising the endosomal pH and inhibiting the fusion of the envelope protein to the endosomal membrane [74, 75] . Similarly, by using a drug repurposing screening of over 6000 molecules, it was found that emricasan, a pan-caspase inhibitor that restrains ZIKV-induced increases in caspase-3 activity and is currently in phase 2 clinical trials in chronic hepatitis C virus (HCV)-infected patients, protected human cortical neural progenitor cells (NPC) in both monolayer and three-dimensional organoid cultures, showing neuroprotective activity without suppression of viral replication [82] . cache = ./cache/cord-273326-gmw8gl2r.txt txt = ./txt/cord-273326-gmw8gl2r.txt === reduce.pl bib === id = cord-262944-9k64f0tw author = Parker, Elaine L. title = Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date = 2020-10-07 pages = extension = .txt mime = text/plain words = 9814 sentences = 497 flesch = 43 summary = In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika virus (ZIKV) at the maternal-fetal interface. We will focus on the viruses human Cytomegalovirus (HCMV) and ZIKV, which are known causes of adverse pregnancy outcomes and delve into how they interact with various decidual immune cells to promote their survival and replication. We will explore further the role that NK cells play in specific viral infections in pregnancy TORCH PATHOGENS HCMV Human cytomegalovirus (HCMV) was first described in 1954 by Margaret Smith, who replicated a virus from two newborn babies who had died from cytomegalic inclusion disease (CID) (41) . A study performed using decidual and chorionic villous tissue from early and mid-gestation human pregnancy shows that ZIKV appears to elevate type I and III IFN expression, which does not occur in HCMV infection (131) . cache = ./cache/cord-262944-9k64f0tw.txt txt = ./txt/cord-262944-9k64f0tw.txt === reduce.pl bib === id = cord-298166-045evk7g author = Röcker, Annika E. title = The molecular tweezer CLR01 inhibits Ebola and Zika virus infection date = 2018-02-08 pages = extension = .txt mime = text/plain words = 5837 sentences = 369 flesch = 58 summary = As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Methods describing the effect of CLR01 on pseudotyped lentiviral particles (2.3.), Ebola virus infection (2.4.), the detection of ZIKV infection by a colorimetric MTT assay (2.5.) or by cell-based ZIKV immunodetection assay (2.6.), flow cytometry (2.7.) and confocal microscopy (2.8.) as well as the RNA release assay (2.9.) and the antiviral activity of CLR01 in body fluids (2.10) can be found in the supplement. cache = ./cache/cord-298166-045evk7g.txt txt = ./txt/cord-298166-045evk7g.txt === reduce.pl bib === id = cord-332473-ec8lu2a3 author = Amorim, Raquel title = Zika virus inhibits eIF2α-dependent stress granule assembly date = 2017-07-17 pages = extension = .txt mime = text/plain words = 6549 sentences = 340 flesch = 51 summary = In cells treated with salubrinal prior to Ars-induced stress, ZIKV-infected cells present higher levels of phospho-eIF2α as compared to mock-infected control (Fig 6C, compare lanes 6 and 8) . Zika virus inhibits stress granule assembly treated mock-infected cells (Fig 6E) . C. Vero cells were infected with ZIKV or mock-infected and treated at 24 hpi with 75 μM salubrinal for 3 h to block the dephosphorylation of eIF2α and then treated with 500 μM Ars for 1 h to induce cellular stress. D. Vero cells were infected with ZIKV or mock-infected and at 24 hpi were treated with 75 μM salubrinal for 3 h and then oxidative stress was induced by treatment with 500 μM Ars for 1 h. Vero cells were infected with ZIKV or mock-infected and treated at 24 hpi with 10 μM sal003 for 3 h to block the dephosphorylation of eIF2α and then treated with 500 μM Ars for 1 h to induce cellular stress. cache = ./cache/cord-332473-ec8lu2a3.txt txt = ./txt/cord-332473-ec8lu2a3.txt === reduce.pl bib === id = cord-330743-o11d0aa1 author = Yu, Xi title = Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date = 2020-05-25 pages = extension = .txt mime = text/plain words = 4470 sentences = 245 flesch = 54 summary = Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Incubation of the culture supernatant but not the bacterial lysates resulted in significant suppression of DENV ( Figure 1B ) and ZIKV ( Figure 1C ) infectivity in Vero cells, indicating that an extracellular effector(s) secreted by Csp_BJ was responsible for viral inhibition. DENV, ZIKV, HSV-1 and SARS-CoV-2 virus stocks were diluted to 50 plaque-forming units (pfu) per ml and incubated untreated or with a serial dilution of the CbAEs in five-fold steps at 37°C for 1 hr before being added onto Vero cell monolayers for 2 hr of infection. cache = ./cache/cord-330743-o11d0aa1.txt txt = ./txt/cord-330743-o11d0aa1.txt === reduce.pl bib === id = cord-321312-hgp2jwbl author = Carvalho, Sandhra M. title = Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions date = 2020-07-10 pages = extension = .txt mime = text/plain words = 1901 sentences = 95 flesch = 43 summary = title: Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions Thus, we designed and developed for the first time, novel bioconjugates made of Ag-In-S@ZnS (ZAIS) fluorescent quantum dots coupled with ZIKA virus via covalent amide bond with carboxymethylcellulose (CMC) biopolymer for labeling and bioimaging the virus-host cell interactions mechanisms through confocal laser scanning microscopy. This work offers relevant insights regarding the profile of the ZIKA virus-nanoparticle conjugates interactions with VERO cells, which can be applied as a nanoplatform to elucidate the infection mechanisms caused by this viral disease. For biolabeling and bioimaging virus-host cell interactions in vitro, ZIKV_ZAIS conjugates were incubated with VERO cells. The QDs conjugated with ZIKV presented higher entry to VERO cells in comparison to reference QD (ZAIS), indicating the possibility of labeling and detection of ZIKV for tracking the viral infection processes including virus entry and transport in cells. ZAIS-CMC fluorescent conjugates showed insights of ZIKA virus-host cell interactions cache = ./cache/cord-321312-hgp2jwbl.txt txt = ./txt/cord-321312-hgp2jwbl.txt === reduce.pl bib === id = cord-319781-6thdg2up author = Payne, Kelly title = Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men date = 2020-07-24 pages = extension = .txt mime = text/plain words = 8233 sentences = 454 flesch = 51 summary = To understand factors that may contribute to viral spread and address long-term health sequelae for survivors, it is important to review evidence regarding viral presence in semen, sexual transmission potential, and possible effects on fertility. We review evidence for the following viruses: Ebola, Zika, West Nile, pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-corona virus-2 (SARS-CoV-2). Then, we present the state of current research regarding presence in semen, sexual transmission, and fertility effects for the Zika virus (ZIKV), Ebola virus (EBOV), West Nile virus (WNV), pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-coronavirus-2 (SARS-CoV-2) ( Table 1) . In this article, we have reviewed the presence in semen, possibility of sexual transmission, and fertility implications of each of the major recent viral pandemics: Zika, Ebola, West Nile, pandemic influenza, SARS, and SARS-CoV-2. cache = ./cache/cord-319781-6thdg2up.txt txt = ./txt/cord-319781-6thdg2up.txt === reduce.pl bib === id = cord-300379-db79kb5c author = Park, Jun-Gyu title = Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid date = 2019-04-12 pages = extension = .txt mime = text/plain words = 5158 sentences = 262 flesch = 53 summary = To quantify the ability of ATA to prevent ZIKV-induced apoptosis, tissue culture supernatants from ZIKV-infected Vero and A549 cells were harvested at 24, 48, and 72 h p.i. to measure the level of apoptotic signal as determined by caspase 3 and 7 activities ( Figure 5B) . ZIKV-infected cells showed FIGURE 4 | Aurintricarboxylic acid inhibition of ZIKV replication: Vero (A) and A549 (B) cells (24-well plate format, 2.5 × 10 5 cells/well, triplicates) were infected (MOI 0.1) with Paraiba/2015. In this study, we demonstrated that ATA (Figure 1 ) has limited toxicity (Figure 2) and an effective and dose-dependent antiviral activity against ZIKV infection (Figures 3, 4) in both monkey kidney epithelial Vero and human alveolar A549 cells. Notably, ATA can prevent ZIKV-induced CPE and apoptosis in both cell lines ( Figure 5 ) and has broad anti-viral activity against representative ZIKV strains from the African (Uganda/1947 and Nigeria/1968) and the Asian/American (Puerto Rico/2015 and French Polynesia/2013) lineages (Figure 6) . cache = ./cache/cord-300379-db79kb5c.txt txt = ./txt/cord-300379-db79kb5c.txt === reduce.pl bib === id = cord-283405-aozxvxxs author = Vermillion, Meghan S. title = Pregnancy and infection: using disease pathogenesis to inform vaccine strategy date = 2018-02-01 pages = extension = .txt mime = text/plain words = 8428 sentences = 431 flesch = 33 summary = Pregnant women, unborn fetuses, and neonates represent three populations of high-risk individuals that can all be simultaneously protected from vaccine-preventable infectious disease with strategic maternal immunization protocols. Third are neonatal and infant infections, which are not considered to pose significant risk to pregnant women or unborn fetuses, but can cause severe, and sometimes fatal disease in neonates and infants that lack protective maternal immunity following birth. Studies in pregnant nonhuman primates have been instrumental for the identification of CD4 + T cell responses as critical for early control of CMV infection and transmission during pregnancy, 100 and studies in guinea pigs have demonstrated that a single-cycle infectious CMV vaccine induces immune responses similar to natural infection and protects against congenital infection. 125 Vaccine candidates have been developed using diverse platforms, including DNA, mRNA, and purified inactivated and live-attenuated virus, many of which have been tested in non-pregnant mouse and nonhuman primate models for their ability to generate immune responses that mimic responses to natural infection and protected against ZIKV challenge. cache = ./cache/cord-283405-aozxvxxs.txt txt = ./txt/cord-283405-aozxvxxs.txt === reduce.pl bib === id = cord-338136-nbtkl5cx author = Clemente, Nuria Sanchez title = Geographies of risk: Emerging infectious diseases and travel health data date = 2020-06-25 pages = extension = .txt mime = text/plain words = 1149 sentences = 60 flesch = 42 summary = Reflecting on the findings of Petridou and colleagues, 1 describing imported ZIKV cases to the UK between 2016-2018, confirmed at the Rare and Imported Pathogens Laboratory, we look back to the 2015-2017 Zika virus (ZIKV) pandemic and reflect on some of the opportunities and limitations presented by data obtained from returning travellers in enhancing understanding of emerging infectious diseases. Given travellers' well-defined temporal windows of potential exposure, improved recollections of risk behaviors, and access to well-resourced travel clinic laboratories, travel health data are uniquely positioned to provide insights into the pathogenesis of emergent infectious diseases. While travel health data has the opportunity to build on this foundation and provide novel insights about emerging infectious agents, the fastest progress will be made through meaningful bi-directional international partnerships built on respectful collaboration, commitments to capacity building, and cooperative efforts to bolster surveillance. Travel Medicine and Infectious Disease requires that all authors sign a declaration of conflicting interests. Travel Medicine and Infectious Disease requires that all authors sign a declaration of conflicting interests. cache = ./cache/cord-338136-nbtkl5cx.txt txt = ./txt/cord-338136-nbtkl5cx.txt === reduce.pl bib === id = cord-310004-h9ixhhzz author = Yuan, Shuofeng title = Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target date = 2020-08-28 pages = extension = .txt mime = text/plain words = 9521 sentences = 502 flesch = 48 summary = A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. To prioritize these five compounds, we evaluated their antiviral efficacy against other emerging viruses and identified ACA as the only inhibitor that exhibited a broad-spectrum antiviral effect against influenza A H1N1, ZIKV, HIV-1, SARS-CoV-2, EV-A71, human adenovirus 5 (AdV5), and severe fever with thrombocytopenia syndrome virus (SFTSV) (Fig. 1C and fig. Using our previously established proximal differentiated threedimensional (3D) human airway organoids (AOs) for predicting the infectivity of influenza viruses in humans (14) , we confirmed that ACA reduced virus replication by >4 logs (Fig. 2D) , with markedly decreased expression of viral nucleoprotein (NP) antigen (Fig. 2E) . cache = ./cache/cord-310004-h9ixhhzz.txt txt = ./txt/cord-310004-h9ixhhzz.txt === reduce.pl bib === id = cord-309275-soffxxqu author = Li, Shuang title = DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1 date = 2020-10-17 pages = extension = .txt mime = text/plain words = 3962 sentences = 223 flesch = 52 summary = title: DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1 KEY FINDINGS: Through human transcriptome array (HTA) we found the defensin alpha 1B (DEFA1B) expression was significantly increased within exosomes isolated from ZIKV infected A549 cells. Further studies demonstrated that DEFA1B interacted with the origin recognition complex 1 (ORC1) which is required to initiate DNA replication during the cell cycle and increased DEFA1B expression decreased the ORC1 level in the cell nuclei. SIGNIFICANCE: Together, our results demonstrated that the anti-ZIKV activity of DEFA1B can be mediated by exosomes, and DEFA1B interacts with ORC1 to retard cell cycles. Both qPCR ( Figure 3K ) and western blot ( Figure 3L ) data showed no significant changes of ZIKV replication between untreated HEK293T cells and cells with up-regulated DEFA1B group. Our data showed the ZIKV induced exosomes could be internalized into recipient cells and inhibit the cells' DNA replication to retard cell cycles. cache = ./cache/cord-309275-soffxxqu.txt txt = ./txt/cord-309275-soffxxqu.txt === reduce.pl bib === id = cord-311007-0i1abjfa author = Schwarz, Megan C. title = Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone date = 2016-09-28 pages = extension = .txt mime = text/plain words = 4857 sentences = 241 flesch = 50 summary = High levels of infectious virus were produced following transfection of the plasmid bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth curve and plaque assay experiments indicated that the MR766 virus resulting from plasmid transfection exhibited growth characteristics that were more similar to its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA-rescued ZIKV. Indeed, sequence analysis of bacterial plasmid clones of these RT-PCRs demonstrated that all products from wild-type plasmid-transfected cell RNA lacked the inserted intron (Fig. 3B) . In contrast to parental virus RT-PCR products (Fig. 3B) , these sequences carried a single silent G3127A mutation that was inserted during intron cloning, which indicated that these RNAs were generated from the MR766 plasmid. The addition of supernatants from wild-type plasmid-transfected or parental virus-infected 293T cells resulted in readily detectable levels of viral proteins. cache = ./cache/cord-311007-0i1abjfa.txt txt = ./txt/cord-311007-0i1abjfa.txt === reduce.pl bib === id = cord-295351-0zr2e8lh author = Mohd Ropidi, Muhammad Izzuddin title = Endoplasmic reticulum: a focal point of Zika virus infection date = 2020-01-20 pages = extension = .txt mime = text/plain words = 7845 sentences = 389 flesch = 35 summary = Following ZIKV infection, the accumulation of misfolded virus polyproteins in the ER lumen overwhelms the ER protein-folding capacity leading to ER stress and triggers the activation of the UPR (Fig. 2) [47] . Following the dissociation of GRP78 that unmasks the GLS, ATF6 translocate to the Golgi apparatus and undergoes sequential proteolytic processing by Fig. 2 ZIKV-induced ER stress initiates host cell unfolded protein response (UPR). ZIKV infection induces ER stress due to the increased amount of unfolded/misfolded viral (red strand) and host cell (grey strand) protein aggregates in the ER lumen. To summarize, ZIKV virus bypasses the UPR by inhibiting stress granules assembly and reticulophagy to ensure continuous viral protein translation and virion production while simultaneously protecting the virus from host cell defense mechanisms. cache = ./cache/cord-295351-0zr2e8lh.txt txt = ./txt/cord-295351-0zr2e8lh.txt === reduce.pl bib === id = cord-290385-0smnl70i author = Chan, Jasper F.W. title = Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease date = 2016-03-03 pages = extension = .txt mime = text/plain words = 8256 sentences = 479 flesch = 45 summary = Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected "congenital Zika syndrome", while causing asymptomatic or mild exanthematous febrile infections which are dengueor rubella-like in infected individuals. ZIKV RNA could be detected in breast milk and saliva of infected women, although replicative virus particles have not been demonstrated 78, 79 Perinatal transmission of other arboviruses, including DENV, CHIKV, WNV, and YFV, has also been reported. 115,120 74/ 8750 (0.8%) patients with suspected ZIKV infection in the French Polynesia outbreak developed neurological syndromes after presenting with a Zika fever-like illness. Zika fever-related death appears to be extremely rare but a number of probable cases have been reported, especially among immunocompromised patients and neonates with suspected congenital ZIKV infection. cache = ./cache/cord-290385-0smnl70i.txt txt = ./txt/cord-290385-0smnl70i.txt === reduce.pl bib === id = cord-294798-ji3p0l4j author = White, Sarah K. title = Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014 date = 2018-05-31 pages = extension = .txt mime = text/plain words = 4792 sentences = 201 flesch = 47 summary = We have previously reported isolation of ZIKV [8] , DENV [9] , Human coronavirus NL63 [10] , and Enterovirus D68 [11] from children in this school cohort; however, the cases/outbreaks in these prior publications did not include CHIKV, or cases within the May-August, 2014, time frame of the current study. Viral genomic RNA that was extracted from CHIKV, DENV1-4, and ZIKV strains that were obtained from the Biodefense and Emerging Infections Research Resource Repository (BEI Resources, Manassas, VA) were used as positive control materials for rtRT-PCR. The six ZIKV sequences obtained in June 2014 from the CHIKV co-infected patients were highly similar (99.9%) to each other and also cluster within a well-supported monophyletic clade, which, interestingly, includes a divergent strain isolated in 2016 from Guadaloupe (Figs 3B and S3B) . cache = ./cache/cord-294798-ji3p0l4j.txt txt = ./txt/cord-294798-ji3p0l4j.txt === reduce.pl bib === id = cord-354546-lgkqwm6u author = Yin, Yingxian title = Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission date = 2016-09-07 pages = extension = .txt mime = text/plain words = 4081 sentences = 220 flesch = 56 summary = 7 By far, Aedes aegypti is considered the principal transmission vector of ZIKV, 8 although Aedes albopictus, which caused several outbreaks of dengue fever in Guangdong Province of South China in the last two decades, may play a role in the spread of this virus because A. These four infected individuals were first confirmed by real-time reversetranscription polymerase chain reaction (RT-PCR) in Baiyun International Airport of Guangzhou, where the youngest one (the son) had developed fever, and the family was then isolated by the local department of public health. 28 A previous study Figure 4 Phylogenetic tree based on E gene sequences of Zika virus isolates. First imported familial ZIKV cases in China Y Yin et al showed that a patient had prolonged shedding of viral RNA in saliva and urine for up to 29 days after symptom onset. In previous research, E gene sequences of ZIKV isolates were usually utilized to construct phylogenetic trees 19 based on experience from molecular study of dengue virus. cache = ./cache/cord-354546-lgkqwm6u.txt txt = ./txt/cord-354546-lgkqwm6u.txt === reduce.pl bib === id = cord-015352-2d02eq3y author = nan title = ESPR 2017 date = 2017-04-26 pages = extension = .txt mime = text/plain words = 82253 sentences = 4479 flesch = 46 summary = Lapierre; Montreal/CA Summary: Objectives: To review the classification of visceroatrial situs To describe the associated cardiac and non-cardiac anomalies To illustrate typical findings in fetuses, neonates and children To discuss the surgical consideration and the long-term follow-up in these patients Abstract: By definition, the type of situs is determined by the relationship between the atria and the adjacent organs. As is often the case, radiology in JIA is all about: knowing your clinicians (i.e. the pretest likelihood for disease) being technically eloquent (e.g. using high-resolution US probes, not delaying post-contrast MRI acquisitions) knowing what is normal (e.g. normal undulations in the articular surface, focal bone marrow signal variation) not being dogmatic about individual observations or measurements interpreting your findings in a clinical context The lecture will demonstrate similarities and differences among joints and modalities in children with variable-severity JIA. cache = ./cache/cord-015352-2d02eq3y.txt txt = ./txt/cord-015352-2d02eq3y.txt === reduce.pl bib === id = cord-345238-p841weif author = Magalhaes, Tereza title = The Endless Challenges of Arboviral Diseases in Brazil date = 2020-05-09 pages = extension = .txt mime = text/plain words = 1663 sentences = 87 flesch = 42 summary = In this Editorial, we list and discuss some of the main challenges faced by the population and public health authorities in Brazil concerning arbovirus infections, including the occurrence of concurrent epidemics like the ongoing SARS-CoV-2/COVID-19 pandemic. Other studies suggest that the atypically low dengue incidence observed after the Zika epidemics in Brazil and other Latin American countries was due, in part, to short-term DENV protection from ZIKV infections [7, 8] . Escalating the problem of arboviral disease surveillance and management, concurrent outbreaks/epidemics of arboviruses and non-arthropod-borne pathogens can further complicate clinical diagnosis and completely overwhelm/saturate the health care system, as we may be seeing now with the pandemic of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lastly, concurrent epidemics like the SARS-CoV-2/COVID-19 or other respiratory pathogens/illnesses can overwhelm health care systems and further complicate clinical-epidemiological diagnoses. cache = ./cache/cord-345238-p841weif.txt txt = ./txt/cord-345238-p841weif.txt === reduce.pl bib === id = cord-326512-iex98lr1 author = Niu, Xuefeng title = Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model date = 2019-05-25 pages = extension = .txt mime = text/plain words = 5654 sentences = 300 flesch = 58 summary = title: Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. The SHM rates of these heavy chains compared with their predicted germline sequences were relatively low, at 4.51% for 7B3H, 3.47% for 1C11H, and 4.17% for 6A6H, which is lower than that of antibodies isolated from annual trivalent inactivated influenza vaccine (TIV) donors [34] and chronic human immunodeficiency virus (HIV)-1 patients (>30%) [27, 35] . In a separate experiment, an unrelated mAb, 2G11, which is specific for H7N9 influenza virus, showed no protective effects on ZIKV-infected neonatal SCID mice (data not shown). Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus cache = ./cache/cord-326512-iex98lr1.txt txt = ./txt/cord-326512-iex98lr1.txt === reduce.pl bib === id = cord-340907-j9i1wlak author = Zarai, Yoram title = Evolutionary selection against short nucleotide sequences in viruses and their related hosts date = 2020-04-27 pages = extension = .txt mime = text/plain words = 8162 sentences = 415 flesch = 45 summary = Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. Figure 3A and B depicts the average number of under-represented sequences of size m ¼ 3, 4, and 5 nucleotides, identified in few subsets of viruses in both the original and random variants of the virus. A sampling analysis that we performed (see Supplementary document, Section 2.8) suggests that the number of under-represented sequences identified in dsDNA viruses matches their genomic size, when compared with RNA viruses. To show that the correspondence between selection against short palindromic sequences in viruses and restriction sites cannot be explained by basic coding region features such as amino-acid content and order, codon usage bias and dinucleotide distribution, we also evaluated the overlap between restriction sites and common under-represented sequences of random variants of viruses. cache = ./cache/cord-340907-j9i1wlak.txt txt = ./txt/cord-340907-j9i1wlak.txt === reduce.pl bib === id = cord-341907-vql8e2j3 author = Wang, Xinyi title = Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine date = 2019-10-27 pages = extension = .txt mime = text/plain words = 7592 sentences = 387 flesch = 55 summary = Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Nevertheless, when coating the ELISA plate with a ZIKV full-length E protein without hFc, significantly high-titer IgG antibodies were induced, particularly in the Alum and MPL-adjuvanted EDIII ( Figure 2C ), suggesting that fusion of hFc to the EDIII subunit vaccine did not affect the generation of ZIKV-specific IgG antibodies. Nevertheless, when coating the ELISA plate with a ZIKV full-length E protein without hFc, significantly high-titer IgG antibodies were induced, particularly in the Alum and MPL-adjuvanted EDIII ( Figure 2C ), suggesting that fusion of hFc to the EDIII subunit vaccine did not affect the generation of ZIKV-specific IgG antibodies. cache = ./cache/cord-341907-vql8e2j3.txt txt = ./txt/cord-341907-vql8e2j3.txt === reduce.pl bib === id = cord-010119-t1x9gknd author = nan title = Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date = 2017-09-04 pages = extension = .txt mime = text/plain words = 230193 sentences = 13234 flesch = 55 summary = Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). cache = ./cache/cord-010119-t1x9gknd.txt txt = ./txt/cord-010119-t1x9gknd.txt ===== Reducing email addresses Creating transaction Updating adr table ===== Reducing keywords cord-002341-v4r5d26a cord-002164-oqc9h2lu cord-002247-e0z5ypii cord-002720-lrkscs71 cord-003187-qdbcdn2j cord-002581-r7mskri0 cord-003041-v9uevz3l cord-002754-xlk4xpv2 cord-003284-hjx2d5rq cord-003403-ypefqm71 cord-003453-p2buyrcj cord-003482-f1uvohf0 cord-004418-08dljap3 cord-004053-nmt221tu cord-009399-6zpkpdzu cord-102612-xx5l8r9e cord-004022-cr0zskcw cord-004020-qtwcbn7m cord-260336-kwzo8puo cord-016796-g4kqqpy1 cord-284646-fhruiw23 cord-272405-jmwn8pdn cord-102279-ena1usqv cord-263868-ewnf96cz cord-253616-7jyui5ca cord-257539-01s21vh0 cord-278286-1xk31726 cord-292830-gcfx1095 cord-273065-peqz7okh cord-300459-tu2xrt9x cord-273326-gmw8gl2r cord-332473-ec8lu2a3 cord-262944-9k64f0tw cord-298166-045evk7g cord-330743-o11d0aa1 cord-321312-hgp2jwbl cord-319781-6thdg2up cord-300379-db79kb5c cord-283405-aozxvxxs cord-338136-nbtkl5cx cord-310004-h9ixhhzz cord-309275-soffxxqu cord-311007-0i1abjfa cord-295351-0zr2e8lh cord-290385-0smnl70i cord-294798-ji3p0l4j cord-354546-lgkqwm6u cord-015352-2d02eq3y cord-345238-p841weif cord-326512-iex98lr1 cord-340907-j9i1wlak cord-010119-t1x9gknd cord-341907-vql8e2j3 cord-102796-rr8qet8c Creating transaction Updating wrd table ===== Reducing urls cord-002341-v4r5d26a cord-002164-oqc9h2lu cord-002720-lrkscs71 cord-009399-6zpkpdzu cord-004418-08dljap3 cord-003284-hjx2d5rq cord-004020-qtwcbn7m cord-004053-nmt221tu cord-102796-rr8qet8c cord-263868-ewnf96cz cord-273065-peqz7okh cord-332473-ec8lu2a3 cord-292830-gcfx1095 cord-260336-kwzo8puo cord-298166-045evk7g cord-273326-gmw8gl2r cord-283405-aozxvxxs cord-310004-h9ixhhzz cord-311007-0i1abjfa cord-309275-soffxxqu cord-294798-ji3p0l4j cord-354546-lgkqwm6u cord-326512-iex98lr1 cord-010119-t1x9gknd Creating transaction Updating url table ===== Reducing named entities cord-002247-e0z5ypii cord-002164-oqc9h2lu cord-002720-lrkscs71 cord-003187-qdbcdn2j cord-003041-v9uevz3l cord-003403-ypefqm71 cord-003284-hjx2d5rq cord-002581-r7mskri0 cord-002754-xlk4xpv2 cord-003453-p2buyrcj cord-003482-f1uvohf0 cord-009399-6zpkpdzu cord-004418-08dljap3 cord-004053-nmt221tu cord-004020-qtwcbn7m cord-004022-cr0zskcw cord-102612-xx5l8r9e cord-102796-rr8qet8c cord-016796-g4kqqpy1 cord-102279-ena1usqv cord-260336-kwzo8puo cord-284646-fhruiw23 cord-263868-ewnf96cz cord-253616-7jyui5ca cord-257539-01s21vh0 cord-272405-jmwn8pdn cord-278286-1xk31726 cord-273065-peqz7okh cord-292830-gcfx1095 cord-273326-gmw8gl2r cord-300459-tu2xrt9x cord-319781-6thdg2up cord-321312-hgp2jwbl cord-298166-045evk7g cord-262944-9k64f0tw cord-300379-db79kb5c cord-330743-o11d0aa1 cord-002341-v4r5d26a cord-332473-ec8lu2a3 cord-283405-aozxvxxs cord-309275-soffxxqu cord-338136-nbtkl5cx cord-310004-h9ixhhzz cord-295351-0zr2e8lh cord-311007-0i1abjfa cord-290385-0smnl70i cord-354546-lgkqwm6u cord-294798-ji3p0l4j cord-345238-p841weif cord-340907-j9i1wlak cord-326512-iex98lr1 cord-341907-vql8e2j3 cord-015352-2d02eq3y cord-010119-t1x9gknd Creating transaction Updating ent table ===== Reducing parts of speech cord-002247-e0z5ypii cord-002164-oqc9h2lu cord-002720-lrkscs71 cord-002341-v4r5d26a cord-003187-qdbcdn2j cord-002581-r7mskri0 cord-002754-xlk4xpv2 cord-003403-ypefqm71 cord-003453-p2buyrcj cord-003482-f1uvohf0 cord-003041-v9uevz3l cord-004418-08dljap3 cord-004053-nmt221tu cord-009399-6zpkpdzu cord-003284-hjx2d5rq cord-102612-xx5l8r9e cord-004020-qtwcbn7m cord-004022-cr0zskcw cord-016796-g4kqqpy1 cord-102796-rr8qet8c cord-102279-ena1usqv cord-260336-kwzo8puo cord-263868-ewnf96cz cord-257539-01s21vh0 cord-273065-peqz7okh cord-278286-1xk31726 cord-253616-7jyui5ca cord-292830-gcfx1095 cord-284646-fhruiw23 cord-300459-tu2xrt9x cord-332473-ec8lu2a3 cord-330743-o11d0aa1 cord-272405-jmwn8pdn cord-298166-045evk7g cord-273326-gmw8gl2r cord-300379-db79kb5c cord-321312-hgp2jwbl cord-309275-soffxxqu cord-338136-nbtkl5cx cord-319781-6thdg2up cord-345238-p841weif cord-262944-9k64f0tw cord-311007-0i1abjfa cord-354546-lgkqwm6u cord-283405-aozxvxxs cord-294798-ji3p0l4j cord-290385-0smnl70i cord-295351-0zr2e8lh cord-326512-iex98lr1 cord-310004-h9ixhhzz cord-341907-vql8e2j3 cord-340907-j9i1wlak cord-015352-2d02eq3y cord-010119-t1x9gknd Creating transaction Updating pos table Building ./etc/reader.txt cord-290385-0smnl70i cord-273326-gmw8gl2r cord-262944-9k64f0tw cord-290385-0smnl70i cord-273326-gmw8gl2r cord-262944-9k64f0tw number of items: 54 sum of words: 612,271 average size in words: 11,338 average readability score: 48 nouns: virus; cells; blood; infection; patients; cell; study; results; transfusion; time; samples; mice; protein; data; antibody; patient; days; donors; viruses; method; group; disease; plasma; units; analysis; cases; conclusion; testing; assay; treatment; number; platelet; studies; system; proteins; levels; antibodies; use; products; type; control; activity; day; replication; findings; brain; donor; response; risk; children verbs: used; shown; perform; including; infected; identified; compared; reporting; associated; based; increased; determine; followed; testing; found; evaluated; detected; reduced; provided; demonstrated; treated; induced; developing; indicated; suggest; collected; observed; require; analyzed; cause; confirm; assess; result; presented; described; inhibit; obtain; received; led; representing; reveals; contain; decreases; transfused; remaining; neutralizes; known; seen; measuring; related adjectives: viral; anti; human; clinical; positive; high; different; significant; specific; negative; non; higher; antiviral; red; first; low; new; infectious; immune; fetal; potential; available; post; single; lower; severe; multiple; molecular; diagnostic; congenital; pregnant; pre; similar; patient; acute; important; normal; possible; pediatric; infected; many; several; effective; recent; whole; total; additional; large; small; mean adverbs: also; however; well; significantly; respectively; previously; therefore; prior; even; often; highly; approximately; recently; especially; still; currently; ns3; first; clinically; statistically; particularly; directly; less; specifically; potentially; furthermore; additionally; moreover; alone; mainly; later; commonly; generally; similarly; relatively; least; subsequently; together; now; briefly; usually; interestingly; rapidly; slightly; likely; successfully; finally; primarily; fully; almost pronouns: we; our; it; their; its; they; i; them; her; he; his; she; us; you; your; one; itself; themselves; cbae-1; my; z004; me; igg4; a129; z2-cy5; z"ikv; srbcs; s; rbcs/100; mrnas; mg; magpixv; imagej; ifitm3; him; epa)registered; e15.5; dnk; c.1136c proper nouns: ZIKV; Zika; RNA; RBC; Study; Design; Case; Studies; Background; Fig; C; Vero; CT; MRI; PCR; US; RT; Blood; DENV; ER; Virus; T; Brazil; PBS; A; EDIII; ABO; M; D; University; RHD; PLT; B; SARS; Rh; HCV; MR; HIV; HLA; CHIKV; Health; West; Center; mg; Figure; USA; Aedes; ACA; Transfusion; TPE keywords: zikv; zika; virus; rna; cell; infection; denv; vero; study; sars; pcr; ediii; brazil; vaccine; supplementary; rgn; pfu; patient; finding; case; aedes; zk7c3; zk2b10; zais; wnv; wbc; vps; usuv; upr; university; type; transfusion; tpe; test; tbk1; table; system; suppl; studies; sponv; sequence; sample; rhd; result; red; rbc; rare; radiol; protein; pregnant one topic; one dimension: zikv file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161441/ titles(s): Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons three topics; one dimension: zikv; blood; patients file(s): https://www.ncbi.nlm.nih.gov/pubmed/32923629/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103096/ titles(s): Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target | Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 | ESPR 2017 five topics; three dimensions: blood transfusion study; zikv virus cells; patients imaging mri; zikv virus zika; clr01 cells antiviral file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/, https://www.ncbi.nlm.nih.gov/pubmed/32923629/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103096/, https://doi.org/10.3390/vaccines7040161, https://www.sciencedirect.com/science/article/pii/S0167577X20309848?v=s5 titles(s): Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 | Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target | ESPR 2017 | Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine | Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions Type: cord title: keyword-zikv-cord date: 2021-05-25 time: 18:11 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:zikv ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-332473-ec8lu2a3 author: Amorim, Raquel title: Zika virus inhibits eIF2α-dependent stress granule assembly date: 2017-07-17 words: 6549 sentences: 340 pages: flesch: 51 cache: ./cache/cord-332473-ec8lu2a3.txt txt: ./txt/cord-332473-ec8lu2a3.txt summary: In cells treated with salubrinal prior to Ars-induced stress, ZIKV-infected cells present higher levels of phospho-eIF2α as compared to mock-infected control (Fig 6C, compare lanes 6 and 8) . Zika virus inhibits stress granule assembly treated mock-infected cells (Fig 6E) . C. Vero cells were infected with ZIKV or mock-infected and treated at 24 hpi with 75 μM salubrinal for 3 h to block the dephosphorylation of eIF2α and then treated with 500 μM Ars for 1 h to induce cellular stress. D. Vero cells were infected with ZIKV or mock-infected and at 24 hpi were treated with 75 μM salubrinal for 3 h and then oxidative stress was induced by treatment with 500 μM Ars for 1 h. Vero cells were infected with ZIKV or mock-infected and treated at 24 hpi with 10 μM sal003 for 3 h to block the dephosphorylation of eIF2α and then treated with 500 μM Ars for 1 h to induce cellular stress. abstract: Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential. During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs). Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG). As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response. In this work, we investigate how ZIKV modulates SG assembly. We demonstrate that ZIKV negatively impacts SG assembly under oxidative stress conditions induced by sodium arsenite (Ars), a treatment that leads to the phosphorylation of eIF2α. By contrast, no measurable difference in SG assembly was observed between mock and ZIKV-infected cells treated with sodium selenite (Se) or Pateamine A (PatA), compounds that trigger eIF2α-independent SG assembly. Interestingly, ZIKV infection markedly impaired the phosphorylation of eIF2α triggered in Ars-treated infected cells, and the abrogation of SG assembly in ZIKV-infected cells is, at least in part, dependent on eIF2α dephosphorylation. These data demonstrate that ZIKV elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication. url: https://www.ncbi.nlm.nih.gov/pubmed/28715409/ doi: 10.1371/journal.pntd.0005775 id: cord-003187-qdbcdn2j author: Bassi, Maria Rosaria title: Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs date: 2018-08-27 words: 6701 sentences: 337 pages: flesch: 41 cache: ./cache/cord-003187-qdbcdn2j.txt txt: ./txt/cord-003187-qdbcdn2j.txt summary: Although the two viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin), while USUV replication is suppressed more efficiently by 5-fluorouracil. We observe that ribavirin, favipiravir, and 5-fluorouracil are all inhibitors of both ZIKV and USUV, and that consecutive passage of virus in the presence of these drugs can lead to the complete extinction of infectivity. To investigate whether ZIKV replication could be affected by increased mutagenesis, we tested four different compounds known to be mutagenic for diverse viruses, 5-fluorouracil, ribavirin, favipiravir, and decitabine (25, 32, 35, (37) (38) (39) . To investigate whether the antiviral activities observed during treatment with favipiravir, ribavirin, and 5-fluorouracil are connected to their predicted mutagenic activity, we analyzed the mutation frequencies of both ZIKV and USUV rescued after 5 passages in the presence of these compounds. abstract: Flaviviruses constitute an increasing source of public health concern, with growing numbers of pathogens causing disease and geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there are currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. In this study, we demonstrate that both viruses are sensitive to three ribonucleosides, favipiravir, ribavirin, and 5-fluorouracil, that have shown mutagenic activity against other RNA viruses while remaining unaffected by a mutagenic deoxyribonucleoside. Serial cell culture passages of ZIKV in the presence of these compounds resulted in the rapid extinction of infectivity, suggesting elevated sensitivity to mutagenesis. USUV extinction was achieved when a 10-fold dilution was applied between every passage, but not in experiments involving undiluted virus, indicating an overall lower susceptibility than ZIKV. Although the two viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin), while USUV replication is suppressed more efficiently by 5-fluorouracil. These differences in sensitivity typically correlate with the increases in the mutation frequencies observed in each nucleoside treatment. These results are relevant to the development of efficient therapies based on lethal mutagenesis and support the rational selection of different mutagenic nucleosides for each pathogen. We will discuss the implications of these results to the fidelity of flavivirus replication and the design of antiviral therapies based on lethal mutagenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125542/ doi: 10.1128/aac.00380-18 id: cord-003453-p2buyrcj author: Batista, Mariana N. title: Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date: 2019-01-11 words: 4157 sentences: 220 pages: flesch: 49 cache: ./cache/cord-003453-p2buyrcj.txt txt: ./txt/cord-003453-p2buyrcj.txt summary: In this study, we tested the activity of the natural compounds berberine and emodin for their ability to inhibit ZIKV infection. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. abstract: Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356660/ doi: 10.3390/v11010049 id: cord-016796-g4kqqpy1 author: Bramhachari, Pallaval Veera title: Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges date: 2019-11-05 words: 5646 sentences: 305 pages: flesch: 34 cache: ./cache/cord-016796-g4kqqpy1.txt txt: ./txt/cord-016796-g4kqqpy1.txt summary: As a part of modern research on immunotechniques, a diagnostic approach for chronic hepatitis C infection (CHC), detects specific antibody to HCV (anti-HCV) (indirect tests) and assays that can detect, quantify, or characterize components of HCV viral particles, viz. Nonetheless, recent studies on respiratory syncytial virus (RSV) developed Luciferase Immunoprecipitation Systems (LIPS) assay to detect IgG Antibodies against Human RSV G-Glycoprotein. Sensitive and specific detection of Crimean-Congo hemorrhagic fever virus (CCHFV) was developed employing specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests (Emmerich et al. A rapid diagnostic platform for colorimetric differential detection of DENV and CHIKV viral infections was recently developed with a possibility to alter clinical diagnosis of acute febrile illnesses in resource-limited settings. This novel antibody demonstrates noteworthy specificity to identify H7N9 virus compared to homemade target-captured ELISA, qRT-PCR, and rapid influenza diagnostic test (RIDT) with high sensitivity (Chang et al. abstract: Diagnosis and identification of viruses is an important component of diagnostic virology laboratory. Although various modes of diagnostic methods are now available at disposal, a vast majority of the diseases across the globe remain undiagnosed. This is largely due to the overlapping undifferentiated set of symptoms across myriad set of RNA and DNA viral diseases. As such, it becomes critical to take into consideration several factors for viral diagnosis ranging from the type and quality of specimen collected, time of specimen collection, mode of transport, accuracy, specificity, sensitivity, and the type of diagnostic method used. This chapter broadly emphasizes various methods on diagnostic virology ranging from the classical methods of diagnosis to the most recently developed molecular methods of detection of virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121190/ doi: 10.1007/978-981-15-1045-8_17 id: cord-321312-hgp2jwbl author: Carvalho, Sandhra M. title: Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions date: 2020-07-10 words: 1901 sentences: 95 pages: flesch: 43 cache: ./cache/cord-321312-hgp2jwbl.txt txt: ./txt/cord-321312-hgp2jwbl.txt summary: title: Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions Thus, we designed and developed for the first time, novel bioconjugates made of Ag-In-S@ZnS (ZAIS) fluorescent quantum dots coupled with ZIKA virus via covalent amide bond with carboxymethylcellulose (CMC) biopolymer for labeling and bioimaging the virus-host cell interactions mechanisms through confocal laser scanning microscopy. This work offers relevant insights regarding the profile of the ZIKA virus-nanoparticle conjugates interactions with VERO cells, which can be applied as a nanoplatform to elucidate the infection mechanisms caused by this viral disease. For biolabeling and bioimaging virus-host cell interactions in vitro, ZIKV_ZAIS conjugates were incubated with VERO cells. The QDs conjugated with ZIKV presented higher entry to VERO cells in comparison to reference QD (ZAIS), indicating the possibility of labeling and detection of ZIKV for tracking the viral infection processes including virus entry and transport in cells. ZAIS-CMC fluorescent conjugates showed insights of ZIKA virus-host cell interactions abstract: The earliest possible diagnosis and understanding of the infection mechanisms play a crucial role in the outcome of fighting viral diseases. Thus, we designed and developed for the first time, novel bioconjugates made of Ag-In-S@ZnS (ZAIS) fluorescent quantum dots coupled with ZIKA virus via covalent amide bond with carboxymethylcellulose (CMC) biopolymer for labeling and bioimaging the virus-host cell interactions mechanisms through confocal laser scanning microscopy. This work offers relevant insights regarding the profile of the ZIKA virus-nanoparticle conjugates interactions with VERO cells, which can be applied as a nanoplatform to elucidate the infection mechanisms caused by this viral disease. url: https://www.sciencedirect.com/science/article/pii/S0167577X20309848?v=s5 doi: 10.1016/j.matlet.2020.128279 id: cord-290385-0smnl70i author: Chan, Jasper F.W. title: Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease date: 2016-03-03 words: 8256 sentences: 479 pages: flesch: 45 cache: ./cache/cord-290385-0smnl70i.txt txt: ./txt/cord-290385-0smnl70i.txt summary: Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected "congenital Zika syndrome", while causing asymptomatic or mild exanthematous febrile infections which are dengueor rubella-like in infected individuals. ZIKV RNA could be detected in breast milk and saliva of infected women, although replicative virus particles have not been demonstrated 78, 79 Perinatal transmission of other arboviruses, including DENV, CHIKV, WNV, and YFV, has also been reported. 115,120 74/ 8750 (0.8%) patients with suspected ZIKV infection in the French Polynesia outbreak developed neurological syndromes after presenting with a Zika fever-like illness. Zika fever-related death appears to be extremely rare but a number of probable cases have been reported, especially among immunocompromised patients and neonates with suspected congenital ZIKV infection. abstract: Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected “congenital Zika syndrome”, while causing asymptomatic or mild exanthematous febrile infections which are dengue- or rubella-like in infected individuals. Despite having been discovered in Uganda for almost 60 years, <20 human cases were reported before 2007. The massive epidemics in the Pacific islands associated with the ZIKV Asian lineage in 2007 and 2013 were followed by explosive outbreaks in Latin America in 2015. Although increased mosquito breeding associated with the El Niño effect superimposed on global warming is suspected, genetic changes in its RNA virus genome may have led to better adaptation to mosquitoes, other animal reservoirs, and human. We reviewed the epidemiology, clinical manifestation, virology, pathogenesis, laboratory diagnosis, management, and prevention of this emerging infection. Laboratory diagnosis can be confounded by cross-reactivity with other circulating flaviviruses. Besides mosquito bite and transplacental transmission, the risk of other potential routes of transmission by transfusion, transplantation, sexual activity, breastfeeding, respiratory droplet, and animal bite is discussed. Epidemic control requires adequate clearance of mosquito breeding grounds, personal protection against mosquito bite, and hopefully a safe and effective vaccine. url: https://www.sciencedirect.com/science/article/pii/S016344531600061X doi: 10.1016/j.jinf.2016.02.011 id: cord-002341-v4r5d26a author: Chan, Jasper Fuk-Woo title: Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons date: 2016-11-12 words: 7155 sentences: 399 pages: flesch: 52 cache: ./cache/cord-002341-v4r5d26a.txt txt: ./txt/cord-002341-v4r5d26a.txt summary: To establish a novel mouse model for ZIKV infection, we compared the clinical, histological, and virological findings of male (group 1) and female (group 2) mice with dexamethasone immunosuppression and ZIKV inoculation with those of the appropriate controls (groups 3 to 8) (Table 1 ). The dexamethasone-immunosuppressed mice with ZIKV inoculation in our study developed disseminated infection with viremia and multi-organ involvement, including the brain, urogenital tract, intestine, liver, spleen, pancreas, heart, lung, and salivary gland as evident by ZIKV-NS1 protein expression on immunohistochemical staining and/or detectable viral load in these tissues. Our findings provided an additional explanation for the pathogenesis of fatal ZIKV infection, which has been proposed to be related to uncontrolled virus dissemination in previously described mouse models utilizing types I/II interferon-signaling-/receptor-deficient mice that were unable to mount a robust host innate immune response. abstract: BACKGROUND: Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. METHODS: We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. RESULTS: Dexamethasone-immunosuppressed male mice (6–8 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥ 10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi. Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P < 0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45 + and CD8 + inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). CONCLUSIONS: Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161441/ doi: 10.1016/j.ebiom.2016.11.017 id: cord-338136-nbtkl5cx author: Clemente, Nuria Sanchez title: Geographies of risk: Emerging infectious diseases and travel health data date: 2020-06-25 words: 1149 sentences: 60 pages: flesch: 42 cache: ./cache/cord-338136-nbtkl5cx.txt txt: ./txt/cord-338136-nbtkl5cx.txt summary: Reflecting on the findings of Petridou and colleagues, 1 describing imported ZIKV cases to the UK between 2016-2018, confirmed at the Rare and Imported Pathogens Laboratory, we look back to the 2015-2017 Zika virus (ZIKV) pandemic and reflect on some of the opportunities and limitations presented by data obtained from returning travellers in enhancing understanding of emerging infectious diseases. Given travellers'' well-defined temporal windows of potential exposure, improved recollections of risk behaviors, and access to well-resourced travel clinic laboratories, travel health data are uniquely positioned to provide insights into the pathogenesis of emergent infectious diseases. While travel health data has the opportunity to build on this foundation and provide novel insights about emerging infectious agents, the fastest progress will be made through meaningful bi-directional international partnerships built on respectful collaboration, commitments to capacity building, and cooperative efforts to bolster surveillance. Travel Medicine and Infectious Disease requires that all authors sign a declaration of conflicting interests. Travel Medicine and Infectious Disease requires that all authors sign a declaration of conflicting interests. abstract: nan url: https://doi.org/10.1016/j.tmaid.2020.101806 doi: 10.1016/j.tmaid.2020.101806 id: cord-102796-rr8qet8c author: Counotte, Michel J title: Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak date: 2020-03-18 words: 3046 sentences: 198 pages: flesch: 56 cache: ./cache/cord-102796-rr8qet8c.txt txt: ./txt/cord-102796-rr8qet8c.txt summary: We are continuously facing new disease outbreaks, including the new coronavirus (SARS-nCoV-2) in December 2019.The objective of this study was to describe the accumulation of evidence during the 2013-2016 Zika virus (ZIKV) outbreak in the Pacific and the Americas related to aetiological causal questions about congenital abnormalities and Guillain-Barre syndrome. In the 2013-2016 ZIKV outbreak, case reports, case series and basic research studies were published first. A strength of this study is the pre-specified hypothesis about the time to publication of aetiological 139 research and the use of data from systematic reviews that had screened and selected studies that 140 addressed the causal relationship between ZIKV infection and its adverse outcomes. The accumulation of evidence over time in new causal problems seems to follow a hierarchy where 225 case reports and case series were rapidly followed by basic research. Syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study abstract: Introduction: Outbreaks of infectious diseases trigger an increase in scientific research and output. Early in outbreaks, evidence is scarce, but it accumulates rapidly. We are continuously facing new disease outbreaks, including the new coronavirus (SARS-nCoV-2) in December 2019.The objective of this study was to describe the accumulation of evidence during the 2013-2016 Zika virus (ZIKV) outbreak in the Pacific and the Americas related to aetiological causal questions about congenital abnormalities and Guillain-Barre syndrome. Methods: We hypothesised that the temporal sequence would follow a pre-specified order, according to study design. We assessed 1) how long it takes before findings from a specific study design appear, 2) how publication of preprints could reduce the time to publication and 3) how time to publication evolves over time. Results: We included 346 publications published between March 6, 2014 and January 1, 2019. In the 2013-2016 ZIKV outbreak, case reports, case series and basic research studies were published first. Case-control and cohort studies appeared between 400-700 days after ZIKV was first detected in the region of the study origin. Delay due to the publication process were lowest at the beginning of the outbreak. Only 4.6% of the publications was available as preprints. Discussion: The accumulation of evidence over time in new causal problems generally followed a hierarchy. Preprints reduced the delay to initial publication. Our methods can be applied to new emerging infectious diseases. url: https://doi.org/10.1101/2020.03.16.20036806 doi: 10.1101/2020.03.16.20036806 id: cord-257539-01s21vh0 author: Delvecchio, Rodrigo title: Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models date: 2016-11-29 words: 5669 sentences: 290 pages: flesch: 52 cache: ./cache/cord-257539-01s21vh0.txt txt: ./txt/cord-257539-01s21vh0.txt summary: Immunofluorescence staining corroborated these results ( Figure 1B ) and additionally, chloroquine decreased the production of infectious ( Figure 1C ) and total ( Figure 1D ) virus particles, including defective viral particles, by ZIKV-infected cells. Incubation of Vero cells with chloroquine at 0 h postinfection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. Incubation of Vero cells with chloroquine at 0 h post-infection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). abstract: Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres. url: https://www.ncbi.nlm.nih.gov/pubmed/27916837/ doi: 10.3390/v8120322 id: cord-004020-qtwcbn7m author: Gao, Yaning title: Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date: 2019-11-02 words: 7693 sentences: 354 pages: flesch: 50 cache: ./cache/cord-004020-qtwcbn7m.txt txt: ./txt/cord-004020-qtwcbn7m.txt summary: A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Gossypol-treated ZIKV was incubated with Vero E6 cells at 37 • C for 1 h in the presence of DMEM containing serial dilutions of each of the other three natural products identified, such as curcumin, digitonin, and conessine, or anti-ZIKV compound control (bortezomib). Based on Table 1 , four "hit" natural products, including gossypol, curcumin, digitonin, and conessine ( Figure 2A -D), were selected, since they demonstrated inhibitory activity against ZIKV infection with no obvious cytotoxicity in Vero E6 cells when observed under a microscope. Since gossypol demonstrated the highest antiviral activity individually against all ZIKV strains tested, we next investigated the potential combinatorial effects of the combination of gossypol with three other natural products identified, namely curcumin, digitonin, and conessine, as well as anti-ZIKV compound control (bortezomib). abstract: Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations. No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases. After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine. Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity. Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains. The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV. In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV. A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro. Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893700/ doi: 10.3390/v11111019 id: cord-273065-peqz7okh author: Girard, Marc title: Arboviruses: A global public health threat date: 2020-04-24 words: 5574 sentences: 241 pages: flesch: 48 cache: ./cache/cord-273065-peqz7okh.txt txt: ./txt/cord-273065-peqz7okh.txt summary: The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs. The recent outbreak of neurological disorders and neonatal malformations associated with Zika virus (ZIKV) infection in Latin America {5}, the yellow fever (YFV) epidemics in Angola and Brazil with importation to China [6] , the ever-expanding West Nile virus (WNV) epidemic in the Americas [7] , the recent emergence in East Africa and global spread of chikungunya virus (CHIKV) [8] , as well as the ongoing and expanding dengue virus (DENV) pandemic in the tropics and subtropics [9] have reinforced the call for action in the fight against emerging and re-emerging arboviral diseases. The vaccine showed high efficacy and good safety in seropositive persons in the 9-45 years age group, but a risk of severe dengue was observed in individuals who were naive for DENV infection at the time they were vaccinated. abstract: A conference on «ARBOVIRUSES, A GLOBAL PUBLIC HEALTH THREAT» was organized on June 20–22, 2018 at the Merieux Foundation Conference Center in Veyrier du Lac, France, to review and raise awareness to the global public health threat of epidemic arboviruses, and to advance the discussion on the control and prevention of arboviral diseases. The presentations by scientists and public health officials from Asia, the Americas, Europe and Africa strengthened the notion that arboviral diseases of both humans and domestic animals are progressively becoming dominant public health problems in the world. The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs. url: https://www.sciencedirect.com/science/article/pii/S0264410X20304709 doi: 10.1016/j.vaccine.2020.04.011 id: cord-004053-nmt221tu author: Goh, Gerard Kian-Meng title: Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity date: 2019-11-06 words: 6456 sentences: 326 pages: flesch: 60 cache: ./cache/cord-004053-nmt221tu.txt txt: ./txt/cord-004053-nmt221tu.txt summary: Percentages of intrinsic disorder (PIDs) of M and C shell proteins from Zika virus (ZIKV) strains with UniProt accession. According to our research on other viruses, the capsid association with virulence involves a mechanism of protein promiscuity, whereby intrinsic disorder allows the capsid protein (the C protein, in the case of flaviviruses) to bind to a greater number of proteins, thereby allowing the virus to multiply more rapidly before the host immune system can take action [2, 14, 51] . It is therefore likely that the different PIDs of C proteins from the various ZIKV strains and lineages are the result of the types of primates that the peculiar ZIKV strain primarily infects and its ability to fine-tune its C disorder to meet the optimal viral load necessary for more efficient transmission of the virus in a given host, as seen in the case of other viruses and other flaviviruses [2, 14, 25, 39, 49, 50] . abstract: Zika virus (ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r(2) = 0.9) and DENV-2 (DENV-2 + ZIKV, r(2) = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r(2) = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920988/ doi: 10.3390/biom9110710 id: cord-292830-gcfx1095 author: Ianevski, Aleksandr title: Novel activities of safe-in-human broad-spectrum antiviral agents date: 2018-04-23 words: 5511 sentences: 298 pages: flesch: 45 cache: ./cache/cord-292830-gcfx1095.txt txt: ./txt/cord-292830-gcfx1095.txt summary: Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. Here, we hypothesised that some of the identified safe-in-human BSAs could possess novel antiviral activities and, therefore, could be used for treatment of many different viral infections. Fig. 1 shows BSAs and other approved antiviral drugs linked to viral and host targets through viruses they inhibit. Thus, we tested several known BSA agents against (−)ssRNA, (+) ssRNA, ssRNA-RT and dsDNA viruses and identified novel activities for dalbavancin against EV1, ezetimibe against ZIKV and HIV-1, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against RVFV. We identified novel antiviral activities for dalbavancin (against EV1), ezetimibe (against HIV-1 and ZIKV), azacitidine, cyclosporine, minocycline, oritavancin and ritonavir (against RVFV) (Fig. 4) . abstract: According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/29698664/ doi: 10.1016/j.antiviral.2018.04.016 id: cord-284646-fhruiw23 author: Jaeger, Anna S. title: Spondweni virus causes fetal harm in Ifnar1(-/-) mice and is transmitted by Aedes aegypti mosquitoes date: 2020-05-24 words: 3948 sentences: 247 pages: flesch: 57 cache: ./cache/cord-284646-fhruiw23.txt txt: ./txt/cord-284646-fhruiw23.txt summary: Vector competence experiments showed that Ae. aegypti could transmit SPONV when 70 exposed to bloodmeal titers that approximate physiological titers, while Cx. quinquefasciatus nonpregnant, mixed sex 6-to 11-week-old mice lacking type I interferon signaling (Ifnar1 -/-) Ar94 (this is the only strain used in these studies, so it will be referred to hereafter as 86 SPONV); or 10 2 PFU of the highly pathogenic African-lineage ZIKV strain DAK AR 41524 87 (ZIKV-DAK) (Jaeger et al., 2019) . Despite significantly higher maternal 141 viremia observed at 4 dpi with ZIKV-DAK-infected dams, the fact that resorption rates did 142 not significantly differ between the two groups indicates that both ZIKV-DAK and SPONV 143 have a propensity to harm the developing fetus that is independent of the amount of 144 replication in maternal blood. In contrast, ZIKV-DAK-and SPONV-inoculated dams displayed 221 varying degrees of placental pathology with severe effects predominantly observed in the 222 the labyrinth zone, including vascular injury involving maternal and/or fetal vascular spaces, 223 infarction (obstructed blood flow), necrosis, apoptosis, and hemorrhage (Fig. 4) . abstract: Spondweni virus (SPONV) is the most closely related known flavivirus to Zika virus (ZIKV). Its pathogenic potential and vector specificity have not been well defined. SPONV has been found predominantly in Africa, but was recently detected in a pool of Culex quinquefasciatus mosquitoes in Haiti. Here we show that SPONV can cause significant fetal harm, including demise, comparable to ZIKV, in a mouse model of vertical transmission. Following maternal inoculation, we detected infectious SPONV in placentas and fetuses, along with significant fetal and placental histopathology, together suggesting vertical transmission. To test vector competence, we exposed Aedes aegypti and Culex quinquefasciatus mosquitoes to SPONV-infected bloodmeals. Aedes aegypti could efficiently transmit SPONV, whereas Culex quinquefasciatus could not. Our results suggest that SPONV has the same features that made ZIKV a public health risk. url: https://api.elsevier.com/content/article/pii/S0042682220300921 doi: 10.1016/j.virol.2020.05.005 id: cord-102612-xx5l8r9e author: Kodani, Andrew title: Zika virus alters centrosome organization to suppress the innate immune response date: 2020-09-15 words: 4895 sentences: 302 pages: flesch: 46 cache: ./cache/cord-102612-xx5l8r9e.txt txt: ./txt/cord-102612-xx5l8r9e.txt summary: ZIKV infection or loss of CEP63 decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection or loss of CEP63 also increased the centrosomal accumulation of the CEP63 interactors, Mindbomb1 (MIB1) and DTX4, ubiquitin ligases that respectively activate and degrade TBK1. In addition to identifying a mechanism by which CEP63 controls the innate immune responses in ZIKV infection, we propose that the altered centrosomal organization caused by altered CEP63 function may contribute to ZIKV-associated microcephaly. ZIKV infection in U87 cells did not affect either the localization or levels of the MCPH-associated proteins PLK4, STIL, SAS6, CDK5RAP2, CEP152, or WDR62 (Supplemental Figure 2A-D) . In summary, we have found that ZIKV NS3 localizes to the centrosome, recruits CEP63 and its binding partners MIB1 and DTX4 to ubiquitylate and degrade TBK1, a key regulator of the innate immune response. abstract: Zika virus (ZIKV) is a flavivirus transmitted via mosquitoes and sex to cause congenital neurodevelopmental defects, including microcephaly. Inherited forms of microcephaly (MCPH) are associated with disrupted centrosome organization. Similarly, we found that ZIKV infection disrupted centrosome organization. ZIKV infection disrupted the organization of centrosomal proteins including CEP63, a MCPH-associated protein. The ZIKV nonstructural protein NS3 bound CEP63, and expression of NS3 was sufficient to alter centrosome architecture and CEP63 localization. Loss of CEP63 suppressed ZIKV-induced centrosome disorganization, indicating that ZIKV requires CEP63 to disrupt centrosome organization. ZIKV infection or loss of CEP63 decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection or loss of CEP63 also increased the centrosomal accumulation of the CEP63 interactors, Mindbomb1 (MIB1) and DTX4, ubiquitin ligases that respectively activate and degrade TBK1. Therefore, we propose that ZIKV NS3 binds CEP63 to increase centrosomal DTX4 localization and destabilization of TBK1, thereby tempering the innate immune response. In addition to identifying a mechanism by which CEP63 controls the innate immune responses in ZIKV infection, we propose that the altered centrosomal organization caused by altered CEP63 function may contribute to ZIKV-associated microcephaly. url: https://doi.org/10.1101/2020.09.15.298083 doi: 10.1101/2020.09.15.298083 id: cord-002164-oqc9h2lu author: Kumar, Ashutosh title: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome date: 2016-08-09 words: 5809 sentences: 256 pages: flesch: 40 cache: ./cache/cord-002164-oqc9h2lu.txt txt: ./txt/cord-002164-oqc9h2lu.txt summary: We, for this important reason, searched for the RARE consensus sequence (5 ′ -AGGTCA-3 ′ ) repeats in the genomic sequences of the ZIKV strains with a hypothesis that the virus might act through disruption of normal retinoic acid signaling mediated by incorporation of these sequences into the DNA of developing host brain cells. In view of (1) the bioinformatic evidence of the presence of RARE sequence repeats in genome sequences of ZIKV strains and in other viruses known to cause congenital brain malformation (Table 3) and (2) confirmed role of retinoic acid in neural tube formation and further brain development mediated through RARE sequences, it is scientifically coherent to assume that a RARE sequence dependent mechanism could be the underlying mechanism of microcephaly seen in ZIKV infected fetuses. abstract: Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)—microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker “retinoic acid” in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977292/ doi: 10.3389/fnhum.2016.00403 id: cord-002720-lrkscs71 author: Kurosaki, Yohei title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification date: 2017-10-18 words: 4950 sentences: 251 pages: flesch: 55 cache: ./cache/cord-002720-lrkscs71.txt txt: ./txt/cord-002720-lrkscs71.txt summary: title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. Therefore, it is difficult to detect ZIKV in blood samples from patients after the acute phase of infection, even with sensitive molecular diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR) 14, 18, 19 . These results suggested that the RT-LAMP assay could be used as a rapid, sensitive diagnostic test for ZIKV, the Tp value (i.e., less than 15 min) can be used as an indicator of the number of RNA copies in each reaction. abstract: The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647432/ doi: 10.1038/s41598-017-13836-9 id: cord-253616-7jyui5ca author: Lai, Zheng-Zong title: Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms date: 2020-09-07 words: 4969 sentences: 286 pages: flesch: 48 cache: ./cache/cord-253616-7jyui5ca.txt txt: ./txt/cord-253616-7jyui5ca.txt summary: To investigate the anti-ZIKV activity of harringtonine, we assessed the inhibition of virus infection in Vero cells with MOI = 0.01 under different concentrations of harringtonine for 48 h. Intracellular viral RNA levels, protein expression levels and virus progeny in supernatants were respectively determined by RT-qPCR, western blotting and fluorescent focus assay (FFA). The dose-dependent anti-ZIKV activities of harringtonine were observed to decrease viral RNA/protein production and progeny yield ( Figure 1B-D) , indicating that virus propagation was suppressed. Harringtonine (625 nM) was administered at different stages of ZIKV infection with MOI = 0.1, and then the levels of ZIKV RNA in cells, as well as virus titers in supernatants, were determined after 24 h treatment. Harringtonine (625 nM) was administered at different stages of ZIKV infection with MOI = 0.1, and then the levels of ZIKV RNA in cells, as well as virus titers in supernatants, were determined after 24 h treatment. abstract: Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain–Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV infection are globally underway, but Food and Drug Administration (FDA)-approved treatments are not available yet. Compounds from Chinese medicinal herbs may offer an opportunity for potential therapies for anti-ZIKV infection. In this study, we evaluated the antiviral efficacy of harringtonine against ZIKV. Harringtonine possessed anti-ZIKV properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection. The antiviral activity also observed in the treatment against Japanese encephalitis reporter virus (RP9-GFP strain). Overall, this study demonstrated that harringtonine would be a favorable potential candidate for the development of anti-ZIKV infection therapies. url: https://www.ncbi.nlm.nih.gov/pubmed/32906689/ doi: 10.3390/molecules25184082 id: cord-300459-tu2xrt9x author: Li, Cui title: A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos date: 2018-05-01 words: 6832 sentences: 353 pages: flesch: 56 cache: ./cache/cord-300459-tu2xrt9x.txt txt: ./txt/cord-300459-tu2xrt9x.txt summary: We previously reported on a panel of monoclonal antibodies (mAbs) derived from the longitudinal samples of a ZIKV-convalescent individual and characterized their neutralizing activities, epitope specificities, and development timeline over the course of infection . Here, we use the mouse models of ZIKV infection and microcephaly to analyze the in vivo protective activities of six human mAbs and compare the findings with our reported in vitro neutralization activity, as measured by plaque reduction neutralization test (PRNT). mAbs that target DIII with potent neutralizing activity have also been isolated by other groups, derived from either infected humans or mice, and have been shown to be effective in various models of ZIKV pathogenesis (Fernandez et al., 2017; Magnani et al., 2017; Robbiani et al., 2017; Stettler et al., 2016; Wang et al., 2017b; Zhao et al., 2016) . abstract: Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine. url: https://api.elsevier.com/content/article/pii/S2211124718305345 doi: 10.1016/j.celrep.2018.04.005 id: cord-309275-soffxxqu author: Li, Shuang title: DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1 date: 2020-10-17 words: 3962 sentences: 223 pages: flesch: 52 cache: ./cache/cord-309275-soffxxqu.txt txt: ./txt/cord-309275-soffxxqu.txt summary: title: DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1 KEY FINDINGS: Through human transcriptome array (HTA) we found the defensin alpha 1B (DEFA1B) expression was significantly increased within exosomes isolated from ZIKV infected A549 cells. Further studies demonstrated that DEFA1B interacted with the origin recognition complex 1 (ORC1) which is required to initiate DNA replication during the cell cycle and increased DEFA1B expression decreased the ORC1 level in the cell nuclei. SIGNIFICANCE: Together, our results demonstrated that the anti-ZIKV activity of DEFA1B can be mediated by exosomes, and DEFA1B interacts with ORC1 to retard cell cycles. Both qPCR ( Figure 3K ) and western blot ( Figure 3L ) data showed no significant changes of ZIKV replication between untreated HEK293T cells and cells with up-regulated DEFA1B group. Our data showed the ZIKV induced exosomes could be internalized into recipient cells and inhibit the cells'' DNA replication to retard cell cycles. abstract: AIMS: Zika virus (ZIKV) infection causes a public health concern because of its potential association with the development of microcephaly. During viral infections, the host innate immune response is mounted quickly to produce some endogenous functional molecules to limit virus replication and spread. Exosomes contain molecules from their cell of origin following virus infection and can enter recipient cells for intercellular communication. Here, we aim to clarify whether ZIKV-induced exosomes can regulate viral pathogenicity by transferring specific RNAs. MAIN METHODS: In this study, exosomes were isolated from the supernatants of A549 cells with or without ZIKV infection. Human transcriptome array (HTA) was performed to analyze the profiling of RNAs wrapped in exosomes. Then qPCR, western blotting and ELISA were used to determine ZIKV replication. CCK-8 and flow cytometry were used to test the cell proliferation and cell cycles. Co-culture assay was used to analyze the effect of exosomes on the cell cycles of recipient cells. KEY FINDINGS: Through human transcriptome array (HTA) we found the defensin alpha 1B (DEFA1B) expression was significantly increased within exosomes isolated from ZIKV infected A549 cells. Additionally, we found that the extracellular DEFA1B exerts significant anti-ZIKV activity, mainly before ZIKV entering host cells. Interestingly, up-regulated DEFA1B retards the cell cycle of host cells. Further studies demonstrated that DEFA1B interacted with the origin recognition complex 1 (ORC1) which is required to initiate DNA replication during the cell cycle and increased DEFA1B expression decreased the ORC1 level in the cell nuclei. Accordingly, DEFA1B-containing exosomes can be internalized by the recipient cells to retard their cell cycles. SIGNIFICANCE: Together, our results demonstrated that the anti-ZIKV activity of DEFA1B can be mediated by exosomes, and DEFA1B interacts with ORC1 to retard cell cycles. Our study provides a novel concept that DEFA1B not only acts as an antiviral molecule during ZIKV infection but also may correlate with cell proliferation by retarding the progression of cell cycles. url: https://www.sciencedirect.com/science/article/pii/S0024320520313175?v=s5 doi: 10.1016/j.lfs.2020.118564 id: cord-102279-ena1usqv author: Long, Rory K. M. title: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date: 2020-06-23 words: 3681 sentences: 275 pages: flesch: 55 cache: ./cache/cord-102279-ena1usqv.txt txt: ./txt/cord-102279-ena1usqv.txt summary: projections of 3D STED image stacks show high intensity ERmoxGFP and Sec61β-GFP labeling in a 89 CER region and low intensity labeling in PER tubules in mock-infected cells ( Figure 1A ), as reported 90 previously by diffraction limited confocal microscopy (3). Density-based segmentation of the ERmoxGFP-96 and Sec61β-GFP-labelled ER of ZIKV-infected cells showed that the higher density crescent-shaped 97 CER region exhibited significant overlap with dsRNA-positive ER structures relative to the rest of 98 the ER ( Figure 1B ). Morphological comparison of the dsRNA-positive and -negative CER of 133 ZIKV-infected cells with the CER of mock-infected cells showed that the CER was composed of a 134 convoluted network of tubules for both the ERmoxGFP-and Sec61β-labeled ER ( Figure 3B ). 3D STED analysis showed a predominant distribution of both NS2B and 149 NS4B to the CER and more particularly to the dense ZIKV-induced crescent-shaped tubular matrix 150 in ERmoxGFP transfected U87 cells ( Figure 5A ). abstract: The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of endoplasmic reticulum (ER) membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to identify ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and may be of use to screen for inhibitors of infection by ER-reorganizing viruses. url: https://doi.org/10.1101/2020.05.12.091611 doi: 10.1101/2020.05.12.091611 id: cord-004022-cr0zskcw author: Lu, Chien-Yi title: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date: 2019-10-31 words: 5532 sentences: 235 pages: flesch: 48 cache: ./cache/cord-004022-cr0zskcw.txt txt: ./txt/cord-004022-cr0zskcw.txt summary: The packaging cells carrying the recombinant plasmid encoding the viral structural proteins are transfected with DNA-launched replicons and then self-replicate viral subgenomes and express all viral proteins, allowing viral assembly and release as SRIPs. Several flavivirus, replicon-based SRIPs, including JEV, dengue virus, West Nile virus, and tick-borne encephalitis virus have been generated and demonstrated as safer vaccine candidates [15] [16] [17] . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . abstract: Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 10(6) TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV’s non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893733/ doi: 10.3390/v11111005 id: cord-345238-p841weif author: Magalhaes, Tereza title: The Endless Challenges of Arboviral Diseases in Brazil date: 2020-05-09 words: 1663 sentences: 87 pages: flesch: 42 cache: ./cache/cord-345238-p841weif.txt txt: ./txt/cord-345238-p841weif.txt summary: In this Editorial, we list and discuss some of the main challenges faced by the population and public health authorities in Brazil concerning arbovirus infections, including the occurrence of concurrent epidemics like the ongoing SARS-CoV-2/COVID-19 pandemic. Other studies suggest that the atypically low dengue incidence observed after the Zika epidemics in Brazil and other Latin American countries was due, in part, to short-term DENV protection from ZIKV infections [7, 8] . Escalating the problem of arboviral disease surveillance and management, concurrent outbreaks/epidemics of arboviruses and non-arthropod-borne pathogens can further complicate clinical diagnosis and completely overwhelm/saturate the health care system, as we may be seeing now with the pandemic of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lastly, concurrent epidemics like the SARS-CoV-2/COVID-19 or other respiratory pathogens/illnesses can overwhelm health care systems and further complicate clinical-epidemiological diagnoses. abstract: In this Editorial, we list and discuss some of the main challenges faced by the population and public health authorities in Brazil concerning arbovirus infections, including the occurrence of concurrent epidemics like the ongoing SARS-CoV-2/COVID-19 pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32397512/ doi: 10.3390/tropicalmed5020075 id: cord-002581-r7mskri0 author: Magnani, Diogo M. title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus date: 2017-06-12 words: 5291 sentences: 313 pages: flesch: 55 cache: ./cache/cord-002581-r7mskri0.txt txt: ./txt/cord-002581-r7mskri0.txt summary: title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the isolation of 18 plasmablast-derived human mAbs, sorted 12 days post onset of symptoms from a ZIKV-patient in São Paulo, Brazil. Interestingly, one of these mAbs (P1F12) exhibited no nucleotide mutations when compared to its corresponding germline sequences, but still recognized a ZIKV immunodominant epitope and neutralized the virus. Virus capture assay and recombinant E protein ELISA P1F12 binding was determined by both virus capture assay (VCA) and recombinant (r)E ELISAs. The VCA plates were coated overnight with the mouse-anti-Flavivirus monoclonal antibody 4G2 (clone D1-4G2-4-15, EMD Millipore) followed by incubation with viral stocks (ZIKV or DENV). Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus abstract: The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) ~ 2 μg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481143/ doi: 10.1371/journal.pntd.0005655 id: cord-003482-f1uvohf0 author: Malmlov, Ashley title: Experimental Zika virus infection of Jamaican fruit bats (Artibeus jamaicensis) and possible entry of virus into brain via activated microglial cells date: 2019-02-04 words: 7503 sentences: 400 pages: flesch: 53 cache: ./cache/cord-003482-f1uvohf0.txt txt: ./txt/cord-003482-f1uvohf0.txt summary: Quantitative probe-based reverse transcription PCR (qRT-PCR) was performed on seruminoculated Vero cell supernatants, serum, brain, lung, liver, spleen, kidney, urinary bladder, prostate and testes from bats from both studies. Brain and testicular tissues stained with both goat polyclonal goat anti-Iba1 (green) and monoclonal 4G-2 flavivirus E specific antibodies (red) showed co-localization (yellow) of ZIKV antigen in cytoplasm of activated microglial cells with their characteristic morphology in the cerebral cortex of infected bats 10 dpi in the time course study and 28 day dpi in the pilot study (Fig 9) . Two bat infection experiments were conducted in this investigation; 1) a pilot study to determine susceptibility of Jamaican fruit bats to ZIKV infection, and 2) a time course study to better understand pathophysiology and chronology of events pertaining to the dynamics of viremia, viral tropism, replication and shedding of the virus in a New World bat species. abstract: The emergence of Zika virus (ZIKV) in the New World has led to more than 200,000 human infections. Perinatal infection can cause severe neurological complications, including fetal and neonatal microcephaly, and in adults there is an association with Guillain-Barré syndrome (GBS). ZIKV is transmitted to humans by Aedes sp. mosquitoes, yet little is known about its enzootic cycle in which transmission is thought to occur between arboreal Aedes sp. mosquitos and non-human primates. In the 1950s and ‘60s, several bat species were shown to be naturally and experimentally susceptible to ZIKV with acute viremia and seroconversion, and some developed neurological disease with viral antigen detected in the brain. Because of ZIKV emergence in the Americas, we sought to determine susceptibility of Jamaican fruit bats (Artibeus jamaicensis), one of the most common bats in the New World. Bats were inoculated with ZIKV PRVABC59 but did not show signs of disease. Bats held to 28 days post-inoculation (PI) had detectable antibody by ELISA and viral RNA was detected by qRT-PCR in the brain, saliva and urine in some of the bats. Immunoreactivity using polyclonal anti-ZIKV antibody was detected in testes, brain, lung and salivary glands plus scrotal skin. Tropism for mononuclear cells, including macrophages/microglia and fibroblasts, was seen in the aforementioned organs in addition to testicular Leydig cells. The virus likely localized to the brain via infection of Iba1(+) macrophage/microglial cells. Jamaican fruit bats, therefore, may be a useful animal model for the study of ZIKV infection. This work also raises the possibility that bats may have a role in Zika virus ecology in endemic regions, and that ZIKV may pose a wildlife disease threat to bat populations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382173/ doi: 10.1371/journal.pntd.0007071 id: cord-295351-0zr2e8lh author: Mohd Ropidi, Muhammad Izzuddin title: Endoplasmic reticulum: a focal point of Zika virus infection date: 2020-01-20 words: 7845 sentences: 389 pages: flesch: 35 cache: ./cache/cord-295351-0zr2e8lh.txt txt: ./txt/cord-295351-0zr2e8lh.txt summary: Following ZIKV infection, the accumulation of misfolded virus polyproteins in the ER lumen overwhelms the ER protein-folding capacity leading to ER stress and triggers the activation of the UPR (Fig. 2) [47] . Following the dissociation of GRP78 that unmasks the GLS, ATF6 translocate to the Golgi apparatus and undergoes sequential proteolytic processing by Fig. 2 ZIKV-induced ER stress initiates host cell unfolded protein response (UPR). ZIKV infection induces ER stress due to the increased amount of unfolded/misfolded viral (red strand) and host cell (grey strand) protein aggregates in the ER lumen. To summarize, ZIKV virus bypasses the UPR by inhibiting stress granules assembly and reticulophagy to ensure continuous viral protein translation and virion production while simultaneously protecting the virus from host cell defense mechanisms. abstract: Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family. It is an arbovirus that can cause congenital abnormalities and is sexually transmissible. A series of outbreaks accompanied by unexpected severe clinical complications have captured medical attention to further characterize the clinical features of congenital ZIKV syndrome and its underlying pathophysiological mechanisms. Endoplasmic reticulum (ER) and ER-related proteins are essential in ZIKV genome replication. This review highlights the subcellular localization of ZIKV to the ER and ZIKV modulation on the architecture of the ER. This review also discusses ZIKV interaction with ER proteins such as signal peptidase complex subunit 1 (SPCS1), ER membrane complex (EMC) subunits, and ER translocon for viral replication. Furthermore, the review covers several important resulting effects of ZIKV infection to the ER and cellular processes including ER stress, reticulophagy, and paraptosis-like death. Pharmacological targeting of ZIKV-affected ER-resident proteins and ER-associated components demonstrate promising signs of combating ZIKV infection and rescuing host organisms from severe neurologic sequelae. url: https://www.ncbi.nlm.nih.gov/pubmed/31959174/ doi: 10.1186/s12929-020-0618-6 id: cord-278286-1xk31726 author: Mutso, Margit title: Basic insights into Zika virus infection of neuroglial and brain endothelial cells date: 2020-04-30 words: 6010 sentences: 324 pages: flesch: 54 cache: ./cache/cord-278286-1xk31726.txt txt: ./txt/cord-278286-1xk31726.txt summary: This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). To characterize infection by different ZIKV strains (MR766, PRVABC59 and BeH819015), brain endothelial cells (hCMEC/D3) and neuroglial olfactory ensheathing cells (hOEC and mOEC) were infected at an m.o.i. of 0.1. To examine the virus persistence in neuroglia and human brain endothelial cell cultures, the viral RNA copy numbers in hCMEC/D3, hOEC and mOEC cells infected with MR766, PRVABC59 and BeH819015 for 2 months were quantified using RT-qPCR (Fig. 6) . abstract: Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain–Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood–brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood. This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). Readouts included infection kinetics, intracellular virus localization, viral persistence and cytokine responses. Although not as high as in Vero cells, viral titres exceeded 10(4) plaque-forming units (p.f.u.) ml(−1) in the endothelial/neuroglial cell types, except hOECs. Despite these substantial titres, a relatively small proportion of neuroglial cells were primarily infected. Immunolabelling of infected cells revealed localization of the ZIKV envelope and NS3 proteins in the cytoplasm; NS3 staining overlapped with that of dsRNA replication intermediate and the endoplasmic reticulum (ER). Infected OECs and endothelial cells produced high levels of pro-inflammatory chemokines. Nevertheless, ZIKV was also able to establish persistent infection in hOEC and hCMEC/D3 cells. Taken together, these results provide basic insights into ZIKV infection of endothelial and neuroglial cells and will form the basis for further study of ZIKV disease mechanisms. url: https://doi.org/10.1099/jgv.0.001416 doi: 10.1099/jgv.0.001416 id: cord-003284-hjx2d5rq author: Márquez-Jurado, Silvia title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date: 2018-10-07 words: 9917 sentences: 409 pages: flesch: 51 cache: ./cache/cord-003284-hjx2d5rq.txt txt: ./txt/cord-003284-hjx2d5rq.txt summary: Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. To analyze the genetic stability of the recombinant ZIKV harboring the point mutation A175V in the coding region of the NS2A protein (rZIKV-RGN-mNS2A), total RNA was purified from Vero cells infected with viruses from passage 1 (P1) to passage 5 (P5) using the RNeasy minikit (Qiagen), according to the manufacturer''s specifications. To investigate whether the reduced RNA synthesis of rZIKV-RGN-mNS2A in Vero cells could result in viral attenuation in vivo, the ability of the mutant virus to induce pathogenesis was analyzed in A129 mice and compared with that of the parental rZIKV-RGN ( Figure 6 ). abstract: The recent outbreaks of Zika virus (ZIKV), its association with Guillain–Barré syndrome and fetal abnormalities, and the lack of approved vaccines and antivirals, highlight the importance of developing countermeasures to combat ZIKV disease. In this respect, infectious clones constitute excellent tools to accomplish these goals. However, flavivirus infectious clones are often difficult to work with due to the toxicity of some flavivirus sequences in bacteria. To bypass this problem, several alternative approaches have been applied for the generation of ZIKV clones including, among others, in vitro ligation, insertions of introns and using infectious subgenomic amplicons. Here, we report a simple and novel DNA-launched approach based on the use of a bacterial artificial chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV strain. The sequence was identified from the brain tissue of an aborted fetus with microcephaly. The BAC clone was fully stable in bacteria and the infectious virus was efficiently recovered in Vero cells through direct delivery of the cDNA clone. The rescued virus yielded high titers in Vero cells and was pathogenic in a validated mouse model (A129 mice) of ZIKV infection. Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. This BAC approach provides a stable and reliable reverse genetic system for ZIKV that will help to identify viral determinants of virulence and facilitate the development of vaccine and therapeutic strategies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212934/ doi: 10.3390/v10100547 id: cord-002754-xlk4xpv2 author: Mögling, Ramona title: Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016 date: 2017-09-07 words: 3936 sentences: 203 pages: flesch: 42 cache: ./cache/cord-002754-xlk4xpv2.txt txt: ./txt/cord-002754-xlk4xpv2.txt summary: title: Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016 To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. To map ZIKV expertise and identify diagnostic capacity and capability gaps in Europe during the initial phase of the PHEIC in February 2016, the European Commission (EC) asked the European Centre for Disease Prevention and Control (ECDC) for a rapid assessment of the capacity of laboratories in Europe to detect ZIKV infections and the specific needs for support. The availability of validation materials, positive controls and personnel were indicated as the main challenges for implementation of ZIKV diagnostics in the reference laboratories of the 30 EU/EEA countries. abstract: With international travel, Zika virus (ZIKV) is introduced to Europe regularly. A country's ability to robustly detect ZIKV introduction and local transmission is important to minimise the risk for a ZIKV outbreak. Therefore, sufficient expertise and diagnostic capacity and capability are required in European laboratories. To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. While the coverage and capacity of ZIKV diagnostics in the EU/EEA national reference laboratories were found to be adequate, the assessment of the quality and needs indicated several crucial points of improvement that will need support at national and EU/EEA level to improve ZIKV preparedness, response and EU/EEA ZIKV surveillance activities. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685210/ doi: 10.2807/1560-7917.es.2017.22.36.30609 id: cord-326512-iex98lr1 author: Niu, Xuefeng title: Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model date: 2019-05-25 words: 5654 sentences: 300 pages: flesch: 58 cache: ./cache/cord-326512-iex98lr1.txt txt: ./txt/cord-326512-iex98lr1.txt summary: title: Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. The SHM rates of these heavy chains compared with their predicted germline sequences were relatively low, at 4.51% for 7B3H, 3.47% for 1C11H, and 4.17% for 6A6H, which is lower than that of antibodies isolated from annual trivalent inactivated influenza vaccine (TIV) donors [34] and chronic human immunodeficiency virus (HIV)-1 patients (>30%) [27, 35] . In a separate experiment, an unrelated mAb, 2G11, which is specific for H7N9 influenza virus, showed no protective effects on ZIKV-infected neonatal SCID mice (data not shown). Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus abstract: The Zika virus (ZIKV) outbreak and its link to microcephaly triggered a public health concern. To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. Three mAbs (7B3, 1C11, and 6A6) that showed the most potent and broad neutralization activities against the African, Asian, and American strains were selected for further analysis. mAb 7B3 showed an IC50 value of 11.6 ng/mL against the circulating American strain GZ02. Epitope mapping revealed that mAbs 7B3 and 1C11 targeted residue K394 of the lateral ridge (LR) epitope of the EDIII domain, but 7B3 has a broader LR epitope footprint and recognizes residues T335, G337, E370, and N371 as well. mAb 6A6 recognized residues D67, K118, and K251 of the EDII domain. Interestingly, although the patient was seronegative for DENV infection, mAb 1C11, originating from the VH3-23 and VK1-5 germline pair, neutralized both ZIKV and DENV1. Administration of the mAbs 7B3, 1C11, and 6A6 protected neonatal SCID mice infected with a lethal dose of ZIKV. This study provides potential therapeutic antibody candidates and insights into the antibody response after ZIKV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/31130109/ doi: 10.1080/22221751.2019.1614885 id: cord-300379-db79kb5c author: Park, Jun-Gyu title: Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid date: 2019-04-12 words: 5158 sentences: 262 pages: flesch: 53 cache: ./cache/cord-300379-db79kb5c.txt txt: ./txt/cord-300379-db79kb5c.txt summary: To quantify the ability of ATA to prevent ZIKV-induced apoptosis, tissue culture supernatants from ZIKV-infected Vero and A549 cells were harvested at 24, 48, and 72 h p.i. to measure the level of apoptotic signal as determined by caspase 3 and 7 activities ( Figure 5B) . ZIKV-infected cells showed FIGURE 4 | Aurintricarboxylic acid inhibition of ZIKV replication: Vero (A) and A549 (B) cells (24-well plate format, 2.5 × 10 5 cells/well, triplicates) were infected (MOI 0.1) with Paraiba/2015. In this study, we demonstrated that ATA (Figure 1 ) has limited toxicity (Figure 2) and an effective and dose-dependent antiviral activity against ZIKV infection (Figures 3, 4) in both monkey kidney epithelial Vero and human alveolar A549 cells. Notably, ATA can prevent ZIKV-induced CPE and apoptosis in both cell lines ( Figure 5 ) and has broad anti-viral activity against representative ZIKV strains from the African (Uganda/1947 and Nigeria/1968) and the Asian/American (Puerto Rico/2015 and French Polynesia/2013) lineages (Figure 6) . abstract: Zika virus (ZIKV) is one of the recently emerging vector-borne viruses in humans and is responsible for severe congenital abnormalities such as microcephaly in the Western Hemisphere. Currently, only a few vaccine candidates and therapeutic drugs are being developed for the treatment of ZIKV infections, and as of yet none are commercially available. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antimicrobial and antiviral activity. In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC(50)) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC(50)) > 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication with similar IC(50). Importantly, the inhibitory effect of ATA on ZIKV infection was effective against strains of the African and Asian/American lineages, indicating that this inhibitory effect was not strain dependent. Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a potential anti-ZIKV therapy for future clinical evaluation. url: https://www.ncbi.nlm.nih.gov/pubmed/31031722/ doi: 10.3389/fmicb.2019.00718 id: cord-262944-9k64f0tw author: Parker, Elaine L. title: Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date: 2020-10-07 words: 9814 sentences: 497 pages: flesch: 43 cache: ./cache/cord-262944-9k64f0tw.txt txt: ./txt/cord-262944-9k64f0tw.txt summary: In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika virus (ZIKV) at the maternal-fetal interface. We will focus on the viruses human Cytomegalovirus (HCMV) and ZIKV, which are known causes of adverse pregnancy outcomes and delve into how they interact with various decidual immune cells to promote their survival and replication. We will explore further the role that NK cells play in specific viral infections in pregnancy TORCH PATHOGENS HCMV Human cytomegalovirus (HCMV) was first described in 1954 by Margaret Smith, who replicated a virus from two newborn babies who had died from cytomegalic inclusion disease (CID) (41) . A study performed using decidual and chorionic villous tissue from early and mid-gestation human pregnancy shows that ZIKV appears to elevate type I and III IFN expression, which does not occur in HCMV infection (131) . abstract: The human decidua and placenta form a distinct environment distinguished for its promotion of immunotolerance to infiltrating semiallogeneic trophoblast cells to enable successful pregnancy. The maternal-fetal interface also successfully precludes transmission of most pathogens. This barrier function occurs in conjunction with a diverse influx of decidual immune cells including natural killer cells, macrophages and T cells. However, several viruses, among other microorganisms, manage to escape destruction by the host adaptive and innate immune system, leading to congenital infection and adverse pregnancy outcomes. In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika virus (ZIKV) at the maternal-fetal interface. Host decidual immune cell responses to these specific pathogens will be considered, along with their interactions with other cell types and the ways in which these immune cells may both facilitate and limit infection at different stages of pregnancy. Neither HCMV nor ZIKV naturally infect commonly used animal models [e.g., mice] which makes it challenging to understand disease pathogenesis. Here, we will highlight new approaches using placenta-on-a-chip and organoids models that are providing functional and physiologically relevant ways to study viral-host interaction at the maternal-fetal interface. url: https://www.ncbi.nlm.nih.gov/pubmed/33117336/ doi: 10.3389/fimmu.2020.522047 id: cord-272405-jmwn8pdn author: Parvez, Mohammad K. title: Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future date: 2017-08-04 words: 4192 sentences: 210 pages: flesch: 43 cache: ./cache/cord-272405-jmwn8pdn.txt txt: ./txt/cord-272405-jmwn8pdn.txt summary: Despite substantial advancements in the understanding of the biology of pathogens, the breakthroughs in prevention, and their effects on public health and the global economy, the emergence of novel pandemic viruses remains an enduring puzzle. This review presents an update on the knowledge of important emerging/re-emerging viral infections worldwide, discussing their possible origin, evolution, natural reservoirs, human adaptations, and risk factors ( Fig. 1 ). To understand this further, a recently isolated HEV genotype 3 from a chronic hepatitis E patient containing a recombinant virus-host RNA genome was shown to infect cultured human, pig, and deer hepatocytes [39] . The field of phylodynamics, combining a modeling framework for host, epidemiological, and molecular data, especially for RNA viruses, shows particular promise for Parvez understanding the patterns of viral evolution during epidemics [40, 41] . Despite landmark advances in understanding the nature and biology of many pathogenic viruses, there is limited knowledge on emerging novel viruses, their potential reservoirs, and their modes of transmission. abstract: Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods. The intricate “host-pathogen-environment” relationship remains the key to understanding the emergence/re-emergence of pathogenic viruses. High population density, rampant constructions, poor sanitation, changing climate, and the introduction of anthropophilic vectors create selective pressure on host-pathogen reservoirs. Nevertheless, the knowledge and understanding of such zoonoses and pathogen diversity in their known non-human reservoirs are very limited. Prevention of arboviral infections using vector control methods has not been very successful. Currently, new approaches to protect against food-borne infections, such as consuming only properly cooked meats and animal products, are the most effective control measures. Though significant progress in controlling human immunodeficiency virus and hepatitis viruses has been achieved, the unpredictable nature of evolving viruses and the rare occasions of outbreaks severely hamper control and preventive modalities. url: https://doi.org/10.1159/000478729 doi: 10.1159/000478729 id: cord-319781-6thdg2up author: Payne, Kelly title: Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men date: 2020-07-24 words: 8233 sentences: 454 pages: flesch: 51 cache: ./cache/cord-319781-6thdg2up.txt txt: ./txt/cord-319781-6thdg2up.txt summary: To understand factors that may contribute to viral spread and address long-term health sequelae for survivors, it is important to review evidence regarding viral presence in semen, sexual transmission potential, and possible effects on fertility. We review evidence for the following viruses: Ebola, Zika, West Nile, pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-corona virus-2 (SARS-CoV-2). Then, we present the state of current research regarding presence in semen, sexual transmission, and fertility effects for the Zika virus (ZIKV), Ebola virus (EBOV), West Nile virus (WNV), pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-coronavirus-2 (SARS-CoV-2) ( Table 1) . In this article, we have reviewed the presence in semen, possibility of sexual transmission, and fertility implications of each of the major recent viral pandemics: Zika, Ebola, West Nile, pandemic influenza, SARS, and SARS-CoV-2. abstract: INTRODUCTION: The 21st century has seen a series of viral pandemics that have collectively infected millions of individuals. To understand factors that may contribute to viral spread and address long-term health sequelae for survivors, it is important to review evidence regarding viral presence in semen, sexual transmission potential, and possible effects on fertility. AIM: To review the current literature regarding the sexual transmissibility of recent viral pandemics and their effects on semen parameters and fertility. We review evidence for the following viruses: Ebola, Zika, West Nile, pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-corona virus-2 (SARS-CoV-2). METHODS: A literature search was conducted to identify relevant studies. Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate. MAIN OUTCOME MEASURES: The main outcome measure of this study was reviewing of peer-reviewed literature. RESULTS: Both the Ebola virus and Zika virus are present in semen, but only the Zika virus shows consistent evidence of sexual transmission. Current evidence does not support the presence of the West Nile virus, pandemic influenza, SARS, and SARS-CoV-2 in semen. The Zika virus appears to alter semen parameters in a way that diminishes fertility, but the effect is likely time limited. The West Nile virus and SARS have been associated with orchitis in a small number of case reports. Viruses that cause febrile illness, such as pandemic influenza, SARS, and SARS-CoV-2, are associated with decreased sperm count and motility and abnormal morphology. SARS and SARS-CoV-2 may interact with angiotensin-converting enzyme 2 receptors present in the testes, which could impact spermatogenesis. CONCLUSIONS: We have reported the presence in semen, sexual transmission potential, and fertility side effects of recent viral pandemics. Overall, semen studies and fertility effects are highly understudied in viral pandemics, and rigorous study on these topics should be undertaken as novel pandemics emerge. Payne K, Kenny P, Scovell JM, et al. Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications for Men. Sex Med Rev 2020;XX:XXX–XXX. url: https://doi.org/10.1016/j.sxmr.2020.06.003 doi: 10.1016/j.sxmr.2020.06.003 id: cord-003403-ypefqm71 author: Roberts, Christine C. title: Assay Challenges for Emerging Infectious Diseases: The Zika Experience date: 2018-10-02 words: 4957 sentences: 248 pages: flesch: 42 cache: ./cache/cord-003403-ypefqm71.txt txt: ./txt/cord-003403-ypefqm71.txt summary: When initial Zika vaccine clinical trials were being designed and launched in response to the outbreak, there were no standardized sets of viral and immunological assays, and no approved diagnostic tests for Zika virus infection. In an outbreak situation, such as with Zika, it is important to have the ability to quickly develop both diagnostic kits for public health purposes and vaccine clinical assays to support pre-clinical studies and early stage clinical trials. Additionally, cross-reactivity in a number of immunological assays and the short time frame in which viremia can be detected in bodily fluids necessitated the institution of an algorithm to confirm ZIKV infection that was based on a combination of risk factors, clinical symptoms and diagnostic test results [71] . Rapid response to an emerging infectious disease-lessons learned from development of a synthetic DNA vaccine targeting Zika virus abstract: From the perspective of vaccine development, it is imperative to accurately diagnose target infections in order to exclude subjects with prior exposure from evaluations of vaccine effectiveness, to track incident infection during the course of a clinical trial and to differentiate immune reactions due to natural infections from responses that are vaccine related. When vaccine development is accelerated to a rapid pace in response to emerging infectious disease threats, the challenges to develop such diagnostic tools is even greater. This was observed through the recent expansion of Zika virus infections into the Western Hemisphere in 2014–2017. When initial Zika vaccine clinical trials were being designed and launched in response to the outbreak, there were no standardized sets of viral and immunological assays, and no approved diagnostic tests for Zika virus infection. The diagnosis of Zika virus infection is still an area of active research and development on many fronts. Here we review emerging infectious disease vaccine clinical assay development and trial execution with a special focus on the state of Zika virus clinical assays and diagnostics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313918/ doi: 10.3390/vaccines6040070 id: cord-298166-045evk7g author: Röcker, Annika E. title: The molecular tweezer CLR01 inhibits Ebola and Zika virus infection date: 2018-02-08 words: 5837 sentences: 369 pages: flesch: 58 cache: ./cache/cord-298166-045evk7g.txt txt: ./txt/cord-298166-045evk7g.txt summary: As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Methods describing the effect of CLR01 on pseudotyped lentiviral particles (2.3.), Ebola virus infection (2.4.), the detection of ZIKV infection by a colorimetric MTT assay (2.5.) or by cell-based ZIKV immunodetection assay (2.6.), flow cytometry (2.7.) and confocal microscopy (2.8.) as well as the RNA release assay (2.9.) and the antiviral activity of CLR01 in body fluids (2.10) can be found in the supplement. abstract: Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule has previously been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Our findings show that CLR01 is a broad-spectrum inhibitor of enveloped viruses with prospects as a preventative microbicide or antiviral agent. url: https://api.elsevier.com/content/article/pii/S0166354217308458 doi: 10.1016/j.antiviral.2018.02.003 id: cord-273326-gmw8gl2r author: Saiz, Juan-Carlos title: Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date: 2018-08-24 words: 7111 sentences: 293 pages: flesch: 34 cache: ./cache/cord-273326-gmw8gl2r.txt txt: ./txt/cord-273326-gmw8gl2r.txt summary: In this line, and contrary to above mentioned report [73] , CQ, an FDA-approved anti-inflammatory 4-aminoquinoline and an autophagy inhibitor widely used as an anti-malaria drug that is administered to pregnant women at risk of exposure to Plasmodium parasites, was shown to have anti-ZIKV activity in different cell types (Vero cells, human brain microvascular endothelial cells (hBMECs), and human neural stem cells (NSCs)), affecting early stages of the viral life cycle, possibly by raising the endosomal pH and inhibiting the fusion of the envelope protein to the endosomal membrane [74, 75] . Similarly, by using a drug repurposing screening of over 6000 molecules, it was found that emricasan, a pan-caspase inhibitor that restrains ZIKV-induced increases in caspase-3 activity and is currently in phase 2 clinical trials in chronic hepatitis C virus (HCV)-infected patients, protected human cortical neural progenitor cells (NPC) in both monolayer and three-dimensional organoid cultures, showing neuroprotective activity without suppression of viral replication [82] . abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, search for antivirals has been a major aim in ZIKV investigations. To do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/30149598/ doi: 10.3390/v10090453 id: cord-311007-0i1abjfa author: Schwarz, Megan C. title: Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone date: 2016-09-28 words: 4857 sentences: 241 pages: flesch: 50 cache: ./cache/cord-311007-0i1abjfa.txt txt: ./txt/cord-311007-0i1abjfa.txt summary: High levels of infectious virus were produced following transfection of the plasmid bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth curve and plaque assay experiments indicated that the MR766 virus resulting from plasmid transfection exhibited growth characteristics that were more similar to its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA-rescued ZIKV. Indeed, sequence analysis of bacterial plasmid clones of these RT-PCRs demonstrated that all products from wild-type plasmid-transfected cell RNA lacked the inserted intron (Fig. 3B) . In contrast to parental virus RT-PCR products (Fig. 3B) , these sequences carried a single silent G3127A mutation that was inserted during intron cloning, which indicated that these RNAs were generated from the MR766 plasmid. The addition of supernatants from wild-type plasmid-transfected or parental virus-infected 293T cells resulted in readily detectable levels of viral proteins. abstract: The recent Zika virus (ZIKV) outbreak has been linked to severe pathogenesis. Here, we report the construction of a plasmid carrying a cytomegalovirus (CMV) promoter-expressed prototype 1947 Uganda MR766 ZIKV cDNA that can initiate infection following direct plasmid DNA transfection of mammalian cells. Incorporation of a synthetic intron in the nonstructural protein 1 (NS1) region of the ZIKV polyprotein reduced viral cDNA-associated toxicity in bacteria. High levels of infectious virus were produced following transfection of the plasmid bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth curve and plaque assay experiments indicated that the MR766 virus resulting from plasmid transfection exhibited growth characteristics that were more similar to its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA-rescued ZIKV. This ZIKV infectious clone will be useful for investigating the genetic determinants of ZIKV infection and pathogenesis and should be amenable to construction of diverse infectious clones expressing reporter proteins and representing a range of ZIKV isolates. IMPORTANCE The study of ZIKV, which has become increasingly important with the recent association of this virus with microcephaly and Guillain-Barré syndrome, would benefit from an efficient strategy to genetically manipulate the virus. This work describes a model system to produce infectious virus in cell culture. We created a plasmid carrying the prototype 1947 Uganda MR766 ZIKV genome that both was stable in bacteria and could produce high levels of infectious virus in mammalian cells through direct delivery of this DNA. Furthermore, growth properties of this rescued virus closely resembled those of the viral isolate from which it was derived. This model system will provide a simple and effective means to study how ZIKV genetics impact viral replication and pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/27704051/ doi: 10.1128/msphere.00246-16 id: cord-260336-kwzo8puo author: Si, Lulu title: A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue date: 2019-09-27 words: 6353 sentences: 337 pages: flesch: 59 cache: ./cache/cord-260336-kwzo8puo.txt txt: ./txt/cord-260336-kwzo8puo.txt summary: Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Student''s unpaired two-tailed t-test was used to monitor the distribution of Z2 in male A129 mouse body and testicular tissue and to analyze the difference of viral RNA level in sera or tissues between Z2-and vehicle-treated A129 mice. ZIKV RNA copies in (A) testes, (B) epididymides, and (C) sperm of Z2-or vehicle-treated ZIKV-infected male A129 mice at day 16 were detected by qRT-PCR. Zika virus infection in the testicular tissue not only damages male testicular tissue, resulting in pathological lesion of testes and epididymides, but also produces ZIKV-infected semen, causing infertility. abstract: Zika virus (ZIKV) was a re-emerging arbovirus associated with Guillain–Barré Syndrome in adult and congenital Zika syndrome in fetus and infant. Although ZIKV was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. ZIKV can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. However, no drug has been approved for prevention or treatment of ZIKV infection, especially infection in male testicular tissue. Previously reported peptide Z2 could inactivate ZIKV, inhibiting ZIKV infection in vitro and in vivo. Importantly, Z2 could inhibit vertical transmission of ZIKV in pregnant mice, reducing ZIKV infection in fetus. Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Thus, Z2, a ZIKV inactivator, could serve as an antiviral agent for treatment of ZIKV infection and attenuation of ZIKV-induced testicular tissue damage. url: https://doi.org/10.3389/fmicb.2019.02250 doi: 10.3389/fmicb.2019.02250 id: cord-002247-e0z5ypii author: Squires, Raynal C title: Preparedness for Zika virus testing in the World Health Organization Western Pacific Region date: 2016-03-31 words: 1568 sentences: 78 pages: flesch: 40 cache: ./cache/cord-002247-e0z5ypii.txt txt: ./txt/cord-002247-e0z5ypii.txt summary: On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern. The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection. A total of 28 surveys to national-level laboratories likely to be tasked with ZIKV testing were distributed to 19 countries in the Region (omitting resource-limited countries with Zika virus testing preparedness in the Western Pacific Region Squires & Konings reporting having this capacity. While this survey reveals a broad availability of molecular diagnostics to support surveillance of ZIKV in the Western Pacific Region, further key roles remain for laboratories in helping to unravel the pathogenicity of the virus and its potential causal role in the observed cases of microcephaly and other neurological disorders. abstract: On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern. Increased surveillance of the virus, including the requirement for laboratory confirmation of infection, was recommended. The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection. The survey indicated that 16/19 (84%) countries had capacity for molecular detection of ZIKV while others facilitated testing through referral. These results suggest that robust laboratory capacity is in place to support ZIKV surveillance in the Western Pacific Region. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052899/ doi: 10.5365/wpsar.2016.7.1.007 id: cord-263868-ewnf96cz author: Srivastava, Mayank title: Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor date: 2020-08-04 words: 7614 sentences: 429 pages: flesch: 52 cache: ./cache/cord-263868-ewnf96cz.txt txt: ./txt/cord-263868-ewnf96cz.txt summary: ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We used the labeled ZIKV to infect Vero cells and interacting proteins were crosslinked at fixed time points to identify the virus-host factors and elucidate the virus entry mechanism (Fig. 1c) . To further investigate whether the strategy was also capable of correlating spatial information with the virus crosslinked proteins, we performed the STRING analysis to determine whether there is statistical overrepresentation of specific genes or proteins in the sample at specific time points and identify proteins specific at the attachment or cellular entry stages ( Supplementary Fig. 6 ). abstract: The outbreak of Zika virus (ZIKV) in 2016 created worldwide health emergency which demand urgent research efforts on understanding the virus biology and developing therapeutic strategies. Here, we present a time-resolved chemical proteomic strategy to track the early-stage entry of ZIKV into host cells. ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We identified Neural Cell Adhesion Molecule (NCAM1) as a potential ZIKV receptor and further validated it through overexpression, knockout, and inhibition of NCAM1 in Vero cells and human glioblastoma cells U-251 MG. Collectively, the strategy can serve as a universal tool to map virus entry pathways and uncover key interacting proteins. url: https://doi.org/10.1038/s41467-020-17638-y doi: 10.1038/s41467-020-17638-y id: cord-009399-6zpkpdzu author: Sun, Fang title: Topology, Antiviral Functional Residues and Mechanism of IFITM1 date: 2020-03-08 words: 5697 sentences: 354 pages: flesch: 57 cache: ./cache/cord-009399-6zpkpdzu.txt txt: ./txt/cord-009399-6zpkpdzu.txt summary: Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Some studies suggest that IFITM proteins may suppress the entry of viruses by inhibiting the hemifusion of viral membrane and host cell membranes [15] or restricting the formation of fusion pores following virus-endosome hemifusion [16] . Alanine scanning and site-directed mutations found that KRRK basic residues were key for the restriction of IFITM proteins on ZIKV and DENV. Significantly, we found that IFITM1 can restrict the release of ZIKV from endosome to cytosol to prevent the entry of viral particles into host cells, which was associated with its inhibition on organelles acidification. abstract: Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-terminus points into the cytoplasm and C-terminus resides extracellularly. Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Similarly, KRRK basic residues of IFITM2/3 also contributed to suppressing ZIKV replication. Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Overall, our study provided topology, antiviral functional residues and the mechanism of interferon-inducible transmembrane proteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150853/ doi: 10.3390/v12030295 id: cord-283405-aozxvxxs author: Vermillion, Meghan S. title: Pregnancy and infection: using disease pathogenesis to inform vaccine strategy date: 2018-02-01 words: 8428 sentences: 431 pages: flesch: 33 cache: ./cache/cord-283405-aozxvxxs.txt txt: ./txt/cord-283405-aozxvxxs.txt summary: Pregnant women, unborn fetuses, and neonates represent three populations of high-risk individuals that can all be simultaneously protected from vaccine-preventable infectious disease with strategic maternal immunization protocols. Third are neonatal and infant infections, which are not considered to pose significant risk to pregnant women or unborn fetuses, but can cause severe, and sometimes fatal disease in neonates and infants that lack protective maternal immunity following birth. Studies in pregnant nonhuman primates have been instrumental for the identification of CD4 + T cell responses as critical for early control of CMV infection and transmission during pregnancy, 100 and studies in guinea pigs have demonstrated that a single-cycle infectious CMV vaccine induces immune responses similar to natural infection and protects against congenital infection. 125 Vaccine candidates have been developed using diverse platforms, including DNA, mRNA, and purified inactivated and live-attenuated virus, many of which have been tested in non-pregnant mouse and nonhuman primate models for their ability to generate immune responses that mimic responses to natural infection and protected against ZIKV challenge. abstract: Vaccination is the mainstay of preventative medicine for many infectious diseases. Pregnant women, unborn fetuses, and neonates represent three at-risk populations that can be simultaneously protected by strategic vaccination protocols. Because the pathogenesis of different infectious microbes varies based on tissue tropism, timing of infection, and host susceptibility, the goals of immunization are not uniform across all vaccines. Mechanistic understanding of infectious disease pathogenesis and immune responses is therefore essential to inform vaccine design and the implementation of appropriate immunization protocols that optimize protection of pregnant women, fetuses, and neonates. url: https://doi.org/10.1038/s41541-017-0042-4 doi: 10.1038/s41541-017-0042-4 id: cord-341907-vql8e2j3 author: Wang, Xinyi title: Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine date: 2019-10-27 words: 7592 sentences: 387 pages: flesch: 55 cache: ./cache/cord-341907-vql8e2j3.txt txt: ./txt/cord-341907-vql8e2j3.txt summary: Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Nevertheless, when coating the ELISA plate with a ZIKV full-length E protein without hFc, significantly high-titer IgG antibodies were induced, particularly in the Alum and MPL-adjuvanted EDIII ( Figure 2C ), suggesting that fusion of hFc to the EDIII subunit vaccine did not affect the generation of ZIKV-specific IgG antibodies. Nevertheless, when coating the ELISA plate with a ZIKV full-length E protein without hFc, significantly high-titer IgG antibodies were induced, particularly in the Alum and MPL-adjuvanted EDIII ( Figure 2C ), suggesting that fusion of hFc to the EDIII subunit vaccine did not affect the generation of ZIKV-specific IgG antibodies. abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses. url: https://doi.org/10.3390/vaccines7040161 doi: 10.3390/vaccines7040161 id: cord-294798-ji3p0l4j author: White, Sarah K. title: Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014 date: 2018-05-31 words: 4792 sentences: 201 pages: flesch: 47 cache: ./cache/cord-294798-ji3p0l4j.txt txt: ./txt/cord-294798-ji3p0l4j.txt summary: We have previously reported isolation of ZIKV [8] , DENV [9] , Human coronavirus NL63 [10] , and Enterovirus D68 [11] from children in this school cohort; however, the cases/outbreaks in these prior publications did not include CHIKV, or cases within the May-August, 2014, time frame of the current study. Viral genomic RNA that was extracted from CHIKV, DENV1-4, and ZIKV strains that were obtained from the Biodefense and Emerging Infections Research Resource Repository (BEI Resources, Manassas, VA) were used as positive control materials for rtRT-PCR. The six ZIKV sequences obtained in June 2014 from the CHIKV co-infected patients were highly similar (99.9%) to each other and also cluster within a well-supported monophyletic clade, which, interestingly, includes a divergent strain isolated in 2016 from Guadaloupe (Figs 3B and S3B) . abstract: In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island. url: https://doi.org/10.1371/journal.pntd.0006505 doi: 10.1371/journal.pntd.0006505 id: cord-354546-lgkqwm6u author: Yin, Yingxian title: Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission date: 2016-09-07 words: 4081 sentences: 220 pages: flesch: 56 cache: ./cache/cord-354546-lgkqwm6u.txt txt: ./txt/cord-354546-lgkqwm6u.txt summary: 7 By far, Aedes aegypti is considered the principal transmission vector of ZIKV, 8 although Aedes albopictus, which caused several outbreaks of dengue fever in Guangdong Province of South China in the last two decades, may play a role in the spread of this virus because A. These four infected individuals were first confirmed by real-time reversetranscription polymerase chain reaction (RT-PCR) in Baiyun International Airport of Guangzhou, where the youngest one (the son) had developed fever, and the family was then isolated by the local department of public health. 28 A previous study Figure 4 Phylogenetic tree based on E gene sequences of Zika virus isolates. First imported familial ZIKV cases in China Y Yin et al showed that a patient had prolonged shedding of viral RNA in saliva and urine for up to 29 days after symptom onset. In previous research, E gene sequences of ZIKV isolates were usually utilized to construct phylogenetic trees 19 based on experience from molecular study of dengue virus. abstract: Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that can potentially threaten South China. A Chinese family of four returning from Venezuela to China was found to be positive for ZIKV when the youngest son's fever was first detected at an airport immigration inspection. They were isolated temporarily in a local hospital in Enping city, Guangdong province, where their clinical data were recorded and urine and saliva were collected to isolate ZIKV and to obtain viral sequences. All of them except the mother presented mild symptoms of rash and fever. Envelope gene sequences from the father, daughter and son were completely identical. Phylogenetic analysis demonstrated that this strain is similar to several imported strains reported in recent months, which are all clustered into a group isolated from 2015 ZIKA outbreaks in Brazil. Together with the climatic features in Venezuela, New York and Guangdong in February, it can be concluded that our subjects are imported cases from Venezuela. With the same viral sequence being shared between family members, neither direct human-to-human nor vector transmission can be ruled out in this study, but the former seems more likely. Although our subjects had mild illness, epidemiologists and public health officials should be aware of the risk of further expansion of ZIKV transmission by local competent vectors. url: https://doi.org/10.1038/emi.2016.100 doi: 10.1038/emi.2016.100 id: cord-004418-08dljap3 author: Young, Ginger title: Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection date: 2020-02-26 words: 4619 sentences: 265 pages: flesch: 53 cache: ./cache/cord-004418-08dljap3.txt txt: ./txt/cord-004418-08dljap3.txt summary: In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. As with neutralizing antibodies, all PIZV doses were immunogenic and no anti-Zika IgG was detected in the control group prior to ZIKV challenge. PIZV elicited a dose dependent neutralizing antibody immune response and an anti-Zika IgG response which correlated with a reduction in ZIKV vRNA post-challenge (Table 2 ). Vaccinating with a broad range of PIZV dose levels enabled us to correlate both neutralizing and anti-Zika IgG antibody titers to protection against ZIKV infection. A Zika RVP assay (Sonnberg et al., manuscript in preparation) was used to determine neutralizing antibody titers in serum following the administration of PIZV (study days 1, 29, 57, and 71), and 30 days post-ZIKV challenge (day 101). abstract: A critical global health need exists for a Zika vaccine capable of mitigating the effects of future Zika epidemics. In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. Indian rhesus macaques received two doses of PIZV at varying concentrations ranging from 0.016 µg − 10 µg and were subsequently challenged with ZIKV six weeks or one year following the second immunization. PIZV induced a dose-dependent immune response that was boosted by a second immunization. Complete protection against ZIKV infection was achieved with the higher PIZV doses of 0.4 µg, 2 µg, and 10 µg at 6 weeks and with 10 ug PIZV at 1 year following vaccination. Partial protection was achieved with the lower PIZV doses of 0.016 µg and 0.08 µg. Based on these data, a neutralizing antibody response above 3.02 log(10) EC50 was determined as a correlate of protection in macaques. PIZV elicited a dose-dependent neutralizing antibody response which is protective for at least 1 year following vaccination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044319/ doi: 10.1038/s41598-020-60415-6 id: cord-330743-o11d0aa1 author: Yu, Xi title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date: 2020-05-25 words: 4470 sentences: 245 pages: flesch: 54 cache: ./cache/cord-330743-o11d0aa1.txt txt: ./txt/cord-330743-o11d0aa1.txt summary: Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Incubation of the culture supernatant but not the bacterial lysates resulted in significant suppression of DENV ( Figure 1B ) and ZIKV ( Figure 1C ) infectivity in Vero cells, indicating that an extracellular effector(s) secreted by Csp_BJ was responsible for viral inhibition. DENV, ZIKV, HSV-1 and SARS-CoV-2 virus stocks were diluted to 50 plaque-forming units (pfu) per ml and incubated untreated or with a serial dilution of the CbAEs in five-fold steps at 37°C for 1 hr before being added onto Vero cell monolayers for 2 hr of infection. abstract: Viruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug. url: https://doi.org/10.1101/2020.05.22.109900 doi: 10.1101/2020.05.22.109900 id: cord-310004-h9ixhhzz author: Yuan, Shuofeng title: Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target date: 2020-08-28 words: 9521 sentences: 502 pages: flesch: 48 cache: ./cache/cord-310004-h9ixhhzz.txt txt: ./txt/cord-310004-h9ixhhzz.txt summary: A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. To prioritize these five compounds, we evaluated their antiviral efficacy against other emerging viruses and identified ACA as the only inhibitor that exhibited a broad-spectrum antiviral effect against influenza A H1N1, ZIKV, HIV-1, SARS-CoV-2, EV-A71, human adenovirus 5 (AdV5), and severe fever with thrombocytopenia syndrome virus (SFTSV) (Fig. 1C and fig. Using our previously established proximal differentiated threedimensional (3D) human airway organoids (AOs) for predicting the infectivity of influenza viruses in humans (14) , we confirmed that ACA reduced virus replication by >4 logs (Fig. 2D) , with markedly decreased expression of viral nucleoprotein (NP) antigen (Fig. 2E) . abstract: Targeting a universal host protein exploited by most viruses would be a game-changing strategy that offers broad-spectrum solution and rapid pandemic control including the current COVID-19. Here, we found a common YxxØ-motif of multiple viruses that exploits host AP2M1 for intracellular trafficking. A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. YxxØ mutation, AP2M1 depletion, or disruption by ACA causes incorrect localization of viral proteins, which is exemplified by the failure of nuclear import of IAV nucleoprotein and diminished endoplasmic reticulum localization of ZIKV-NS3 and enterovirus-A71-2C proteins, thereby suppressing viral replication. Our study reveals an evolutionarily conserved mechanism of protein-protein interaction between host and virus that can serve as a broad-spectrum antiviral target. url: https://www.ncbi.nlm.nih.gov/pubmed/32923629/ doi: 10.1126/sciadv.aba7910 id: cord-340907-j9i1wlak author: Zarai, Yoram title: Evolutionary selection against short nucleotide sequences in viruses and their related hosts date: 2020-04-27 words: 8162 sentences: 415 pages: flesch: 45 cache: ./cache/cord-340907-j9i1wlak.txt txt: ./txt/cord-340907-j9i1wlak.txt summary: Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. Figure 3A and B depicts the average number of under-represented sequences of size m ¼ 3, 4, and 5 nucleotides, identified in few subsets of viruses in both the original and random variants of the virus. A sampling analysis that we performed (see Supplementary document, Section 2.8) suggests that the number of under-represented sequences identified in dsDNA viruses matches their genomic size, when compared with RNA viruses. To show that the correspondence between selection against short palindromic sequences in viruses and restriction sites cannot be explained by basic coding region features such as amino-acid content and order, codon usage bias and dinucleotide distribution, we also evaluated the overlap between restriction sites and common under-represented sequences of random variants of viruses. abstract: Viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, while evading its immune system. Understanding how viruses co-evolve with their hosts is a fundamental topic in molecular evolution and may also aid in developing novel viral based applications such as vaccines, oncologic therapies, and anti-bacterial treatments. Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. These sequences cannot be explained by the coding regions’ amino acid content, codon, and dinucleotide frequencies. We specifically show that short homooligonucleotide and palindromic sequences tend to be under-represented in many viruses probably due to their effect on gene expression regulation and the interaction with the host immune system. In addition, we show that more sequences tend to be under-represented in dsDNA viruses than in other viral groups. Finally, we demonstrate, based on in vitro and in vivo experiments, how under-represented sequences can be used to attenuated Zika virus strains. url: https://www.ncbi.nlm.nih.gov/pubmed/32339222/ doi: 10.1093/dnares/dsaa008 id: cord-003041-v9uevz3l author: Zukor, Katherine title: Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice date: 2018-02-23 words: 8909 sentences: 454 pages: flesch: 51 cache: ./cache/cord-003041-v9uevz3l.txt txt: ./txt/cord-003041-v9uevz3l.txt summary: This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizurelike activity during the acute phase of disease. This study demonstrates that a contemporary strain of ZIKV (PRVABC59) can widely infect astrocytes and neurons in the brain and spinal cord of adult AG129 mice and cause rapidly progressing hindlimb paralysis, as well as severe seizure activity, during the acute phase of disease. abstract: Zika virus (ZIKV) has received widespread attention because of its effect on the developing fetus. It is becoming apparent, however, that severe neurological sequelae, such as Guillian-Barrë syndrome (GBS), myelitis, encephalitis, and seizures can occur after infection of adults. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. The severity of hindlimb motor deficits correlated with increased numbers of ZIKV-infected lumbosacral spinal motor neurons and decreased numbers of spinal motor neurons. Electrophysiological compound muscle action potential (CMAP) amplitudes in response to stimulation of the lumbosacral spinal cord were reduced when obvious motor deficits were present. ZIKV immunoreactivity was high, intense, and obvious in tissue sections of the brain and spinal cord. Infection in the brain and spinal cord was also associated with astrogliosis as well as T cell and neutrophil infiltration. CMAP and histological analysis indicated that peripheral nerve and muscle functions were intact. Consequently, motor deficits in these circumstances appear to be primarily due to myelitis and possibly encephalitis as opposed to a peripheral neuropathy or a GBS-like syndrome. Thus, acute ZIKV infection of adult AG129 mice may be a useful model for ZIKV-induced myelitis, encephalitis, and seizure activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13365-017-0595-z) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992253/ doi: 10.1007/s13365-017-0595-z id: cord-010119-t1x9gknd author: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 words: 230193 sentences: 13234 pages: flesch: 55 cache: ./cache/cord-010119-t1x9gknd.txt txt: ./txt/cord-010119-t1x9gknd.txt summary: Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/ doi: 10.1111/trf.14286 id: cord-015352-2d02eq3y author: nan title: ESPR 2017 date: 2017-04-26 words: 82253 sentences: 4479 pages: flesch: 46 cache: ./cache/cord-015352-2d02eq3y.txt txt: ./txt/cord-015352-2d02eq3y.txt summary: Lapierre; Montreal/CA Summary: Objectives: To review the classification of visceroatrial situs To describe the associated cardiac and non-cardiac anomalies To illustrate typical findings in fetuses, neonates and children To discuss the surgical consideration and the long-term follow-up in these patients Abstract: By definition, the type of situs is determined by the relationship between the atria and the adjacent organs. As is often the case, radiology in JIA is all about: knowing your clinicians (i.e. the pretest likelihood for disease) being technically eloquent (e.g. using high-resolution US probes, not delaying post-contrast MRI acquisitions) knowing what is normal (e.g. normal undulations in the articular surface, focal bone marrow signal variation) not being dogmatic about individual observations or measurements interpreting your findings in a clinical context The lecture will demonstrate similarities and differences among joints and modalities in children with variable-severity JIA. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103096/ doi: 10.1007/s00247-017-3820-2 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel