# ent

id: cord-276364-zyw5aukk
type: CL
entity:
  positivestrand RNA viruses Dengue and Zika viruses subvert reticulophagy by NS2B3 mediated cleavage of FAM134B Coxsackievirus


id: cord-300648-ixiam7qr
type: CELL_LINE
entity:
  HUVEC HUVEC siNC cells HUVEC siIFITM3 cells IFN α treated 293T cells 293T IFN 293T IFITM3 cells 293T Vector cells


id: cord-300648-ixiam7qr
type: PROTEIN
entity:
  primary antibodies monoclonal anti IFITM1 monoclonal anti IFITM2 polyclonal anti IFITM3 Proteintech Group Chicago IL monoclonal anti


id: cord-300648-ixiam7qr
type: CELL_LINE
entity:
  HUVEC HUVEC siNC IFITM3 siRNA 1 transfected HUVEC HUVEC siIFITM3 IFITM3 transfected 293T cells 293T IFITM3 control vector transfected 293T cells 293T Vector IFN α treated 293T cells 100 U ml 1 293T IFN and 293T cells


id: cord-002179-v8lpw4r7
type: PROTEIN
entity:
  DENV host factors polypyrimidine tract binding protein 1 PTBP1 interleukin enhancer binding factor 3 ILF3 calreticulin CALR calnexin


id: cord-002179-v8lpw4r7
type: PROTEIN
entity:
  octamer binding protein NONO Embryonic stem cell specific 5 hydroxymethylcytosine binding protein HMCES RBMX RNA binding motif protein X chromosome hnRNP M


id: cord-277547-2vim1wno
type: ORG
entity:
  Intracellular Accumulation of Quercetin by Protection of the Chemically or Metabolically Susceptible Hydroxyl Groups


id: cord-318614-518giv0m
type: LAW
entity:
  PCR Evaluation and Clinical Validation of Two Field Deployable Reverse Transcription Insulated Isothermal PCR Assays


id: cord-286255-ded5t1ai
type: GGP
entity:
  malaria 9 11 12 13 18 and typhoid fever 9 10 12 13 15 were not part of our diagnostic algorithm as they are only occasionally


id: cord-002581-r7mskri0
type: ORG
entity:
  Microcephaly Brazil Interim Guidelines for the Evaluation and Testing of Infants with Possible Congenital Zika Virus Infection United States Interim Guidelines for Pregnant Women During a Zika Virus Outbreak United States Human


id: cord-002581-r7mskri0
type: CHEMICAL
entity:
  Nieto Lucas Avelino Silva Vivian I Trindade Mateus Nogueira Juliana Oliveira Consuelo S Maestri Alvino Felix Alvina


id: cord-002581-r7mskri0
type: DISEASE
entity:
  somatic mutations Class switch recombination and somatic hypermutation of virus neutralizing antibodies


id: cord-011968-abd891ej
type: PROTEIN
entity:
  phosphatidylinositol 3 kinase mitogen activated protein kinase kinase extracellular signal regulated kinase c Jun N terminal kinase PI3K MEK


id: cord-276718-3lujp0oy
type: CL
entity:
  stem lengths and cauliflower like structures with multiple loops formed by annealing between alternately inverted repeats of the target sequence


id: cord-025181-eg108wcd
type: DNA
entity:
  DENV 3 0 UTR Forward 5 0 TGAYAAGCARTCAGACAC 3 0 Reverse 5 0 TCAC CARRCTCCCTTTGC 3 0 Fluorescence probe 5 0 CCA GAGATCCTGCTGTCTC 3 0


id: cord-285538-3ah05ijf
type: TAXON
entity:
  Mtb Mycobacterium leprae Legionella pneumophila Listeria monocytogenes Brucella spp Salmonella spp Shigella spp Coxiella burnetii Anaplasma phagocytophilum


id: cord-320091-2lrqubdl
type: ORG
entity:
  the American Society of Tropical Medicine and Hygiene and Open Forum Infectious Diseases Infectious Diseases Society of America


id: cord-317169-qlqavi4t
type: TAXON
entity:
  mengovirus herpes simplex parainfluenza type 3 pseudorabies respiratory syncytial and Sindbis viruses


id: cord-355489-tkvfneje
type: DNA
entity:
  primer DEN1S2133 5 GGAAAATGTTYGAAGCAACYG CCC 3 DEN1AS2553 5 TCCTCCCATGCCTTCC CRATGG 3 and 2 5 U of Taq DNA Polimerase Invotrogene


id: cord-355489-tkvfneje
type: DNA
entity:
  Tree View Program 58 In addition estimated rate of evolutionary change nucleotide substitutions per site


id: cord-355489-tkvfneje
type: WORK_OF_ART
entity:
  Mosquitoes Put the Brake on Arbovirus Evolution Experimental Evolution Reveals Slower MutationAccumulation


id: cord-290385-0smnl70i
type: PROTEIN
entity:
  lactate dehydrogenase aspartate aminotransferase g glutamyl transferase fibrinogen ferritin C reactive protein


id: cord-290385-0smnl70i
type: DISEASE
entity:
  coronaviruses severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus influenza viruses and Ebola virus 2e11


id: cord-294842-aesiff1f
type: CHEMICAL
entity:
  N terminal amphipathic α helices a highly hydrophobic central core domain composed of four putative transmembrane segments


id: cord-307219-okvvajms
type: ORG
entity:
  Nîmes European Centre for Disease Prevention and Control ECDC European Centre for Disease Prevention and Control ECDC Infection


id: cord-355610-7xy4s483
type: PROTEIN
entity:
  mouse anti c Myc antibody Roche Alexa 488 conjugated goat anti mouse antibody Invitrogen and PE conjugated streptavidin Invitrogen


id: cord-345898-a6vt8kso
type: PROTEIN
entity:
  R reporter protein S structural protein NS non structural protein RV recombinant virus RVP reporter virus particle Pro Protease Rep Replicase Q


id: cord-353241-ityhcak7
type: ORG
entity:
  ACAAGTAGAACAACCTGGTCCATACACGCCAAACATGAATGGATG ACAACGGAAGACATGCTGACAGTCTGGAACAGGGTGTGGATTCAAGA AAACCCATGGATGGAAGACAAAACTCCAGTGGAATCATGGGAGGAAA TCCCATACTTGGGAAAAAGAGAAGACCAATGGTGCGGC


id: cord-353241-ityhcak7
type: ORG
entity:
  the China Cancer Society s Cancer Mark Professional Committee the Shaanxi Provincial Cell Biology Society


id: cord-342157-qjyooq68
type: PROTEIN
entity:
  V V I I I I II II II II II III III III T E 148 V I I I I 115 V I I I I 190 L F F F F NS4B 116 V I I I I 191 L


id: cord-355906-yeaw9nr8
type: PROTEIN
entity:
  human leukocyte antigen class I and class II genes tumor necrosis factor alpha FcGRIIA vitamin D receptor transporters


id: cord-355906-yeaw9nr8
type: PROTEIN
entity:
  NS3 helicase nucleoside triphosphatase NTPase RNA 5 triphosphatase RTPase NS5 methyl transferase RNA


id: cord-355906-yeaw9nr8
type: DISEASE
entity:
  respiratory syncytial virus hepatitis viruses influenza virus poliovirus and HIV 109 110 Low molecular weight phenolic


id: cord-282204-j1slaefb
type: ORG
entity:
  Public Health Laboratories Chikungunya Virus Geographic Distribution Infectious Diseases Related to Travel Mosquito


id: cord-282204-j1slaefb
type: ORG
entity:
  Guidelines on Clinical Management of Chikungunya Fever Guidelines on Clinical Management Monitoring and Managing Insecticide Resistance


# bib

id: cord-002085-e7xwb03g
title: DGV: Dengue Genographic Viewer
author: Yamashita, Akifumi
date: 2016-06-07
txt: ./txt/cord-002085-e7xwb03g.txt
cache: ./cache/cord-002085-e7xwb03g.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894901/
doi: 10.3389/fmicb.2016.00875
summary:
  We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. The second database is the Dengue virus genotyping database 2 (Yamashita et al., 2013) , which provides a summary table containing the DENV serotype/genotype, year and country of collection and accession number. The Dengue Virus Resource 3 facilitates the retrieval of DENV sequences deposited in GenBank according to serotype, disease symptom, host, region/country, genome region, and collection and/or release data (Resch et al., 2009) . DGV provides a search engine for the assignment of the DENV serotype, genotype, and origin country according to the most homologous sequence on the basis of a blastn search against the DENV database.

abstract:
  Dengue viruses (DENVs) and their vectors are widely distributed throughout the tropical and subtropical regions of the world. An autochthonous case of DENV was reported in Tokyo, Japan, in 2014, for the first time in 70 years. A comprehensive database of DENV sequences containing both serotype and genotype data and epidemiological data is crucial to trace DENV outbreak isolates and promptly respond to outbreaks. We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. We also implemented the web service Dengue Genographic Viewer (DGV), which shows the geographical distribution of each DENV genotype in a user-specified time span. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. DGV also shows the distribution of DENV-infected entrants to Japan by plotting epidemiological data from the Infectious Agents Surveillance Report (IASR), Japan. This overview of the DENV genotype distribution may aid in planning for the control of DENV infections. DGV is freely available online at: (https://gph.niid.go.jp/geograph/dengue/content/genomemap).


id: cord-002179-v8lpw4r7
author: Viktorovskaya, Olga V.
date: 2016-08-24
txt: ./txt/cord-002179-v8lpw4r7.txt
cache: ./cache/cord-002179-v8lpw4r7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996428/
doi: 10.1371/journal.pntd.0004921
summary:
  title: Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements Previously, we have described a high-throughput mass spectrometry method termed TUX-MS (thiouracil cross-linking mass spectrometry) to identify host factors that interact with viral RNA during a live infection in cell culture [15] . Development of a quantitative thiouridine cross-linking mass spectrometry (qTUX-MS) method for identification of proteins associated with the DENV RNA TUX-MS can be used to identify host factors by incorporating 4-thiouridine (4sU), a zero-distance cross-linker, into the viral RNA (vRNA) to enable cross-linking of proteins bound to vRNA during a live infection in cell culture [15] . Since some of hnRNPs are known to modulate cellular gene expression in response to dengue infection [60, 61] , we can not rule out that some of the observed effects on virus titers derive from their roles in regulating host mRNAs. Among the numerous qTUX-MS identified factors of interest, our study is the first to demonstrate the involvement of HMCES (or C3orf37) in viral infection.

title:
  Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

abstract:
  BACKGROUND: There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. CONCLUSIONS/SIGNIFICANCE: The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.


id: cord-002413-795wuqz5
author: Balinsky, Corey A.
date: 2017-02-14
txt: ./txt/cord-002413-795wuqz5.txt
cache: ./cache/cord-002413-795wuqz5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309953/
doi: 10.1128/jvi.01606-16
summary:
  title: IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10 IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA. FLJ11286, which we refer to here as IRAV (interferon-regulated antiviral gene) (also annotated as C19orf66, UPF0515, or RyDEN), encodes a protein 291 amino acids (aa) in length with a calculated molecular mass of 33.1 kDa. Analysis of published microarray data suggests that IRAV (FLJ11286) is upregulated in response to type I and type II IFNs (6, 20, (24) (25) (26) . IRAV also associates with the host RNA binding proteins UPF1 and HuR (ELAV1) and interacts with MOV10 (a RISC complex RNA helicase), suggesting a role for IRAV in processing or stability of RNA.

title:
  IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10

abstract:
  Dengue virus (DENV) is a member of the genus Flavivirus and can cause severe febrile illness. Here, we show that FLJ11286, which we refer to as IRAV, is induced by DENV in an interferon-dependent manner, displays antiviral activity against DENV, and localizes to the DENV replication complex. IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA. After DENV infection, IRAV, along with MOV10 and Xrn1, localizes to the DENV replication complex and associates with DENV proteins. Depletion of IRAV or MOV10 results in an increase in viral RNA. These data serve to characterize an interferon-stimulated gene with antiviral activity against DENV, as well as to propose a mechanism of activity involving the processing of viral RNA. IMPORTANCE Dengue virus, a member of the family Flaviviridae, can result in a life-threatening illness and has a significant impact on global health. Dengue virus has been shown to be particularly sensitive to the effects of type I interferon; however, little is known about the mechanisms by which interferon-stimulated genes function to inhibit viral replication. A better understanding of the interferon-mediated antiviral response to dengue virus may aid in the development of novel therapeutics. Here, we examine the influence of the interferon-stimulated gene IRAV (FLJ11286) on dengue virus replication. We show that IRAV associates with P bodies in uninfected cells and with the dengue virus replication complex after infection. IRAV also interacts with MOV10, depletion of which is associated with increased viral replication. Our results provide insight into a newly identified antiviral gene, as well as broadening our understanding of the innate immune response to dengue virus infection.


id: cord-002426-5e1xn7kj
author: Falcón-Lezama, Jorge Abelardo
date: 2017-02-22
txt: ./txt/cord-002426-5e1xn7kj.txt
cache: ./cache/cord-002426-5e1xn7kj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321279/
doi: 10.1371/journal.pone.0172313
summary:
  MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority''s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Sample: 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with age older than 12, and residents in Axochiapan, Morelos State, México, were selected from the cohort "Peridomestic infection as determinant for Dengue virus transmission" [13] .

title:
  Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico

abstract:
  INTRODUCTION: Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. RESULTS: Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.


id: cord-002581-r7mskri0
title: A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus
author: Magnani, Diogo M.
date: 2017-06-12
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481143/
doi: 10.1371/journal.pntd.0005655
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.


id: cord-011012-5mev3otu
title: Production and immunogenicity of Fubc subunit protein redesigned from DENV envelope protein
author: Rathore, Abhishek Singh
date: 2020-03-30
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223326/
doi: 10.1007/s00253-020-10541-y
abstract:
  Dengue virus (DENV) is a vector-borne human pathogen that usually causes dengue fever; however, sometime it leads to deadly complications such as dengue with warning signs (DWS+) and severe dengue (SD). Several studies have shown that fusion (Fu) and bc loop of DENV envelope domain II are highly conserved and consist some of the most dominant antigenic epitopes. Therefore, in this study, Fu and bc loops were joined together to develop a short recombinant protein as an alternative of whole DENV envelope protein, and its immunogenic potential as fusion peptide was estimated. For de novo designing of the antigen, Fu and bc peptides were linked with an optimised linker so that the three dimensional conformation was maintained as it is in DENV envelope protein. The redesigned Fubc protein was expressed in E. coli and purified. Subsequently, structural integrity of the purified protein was verified by CD spectroscopy. To characterise immune responses against recombinant Fubc protein, BALB/c mice were subcutaneously injected with emulsified antigen preparation. It was observed by ELISA that Fubc fusion protein elicited higher serum IgG antibody response either in the presence or in absence of Freund’s adjuvant in comparison to the immune response of Fu and bc peptides separately. Furthermore, the binding of Fubc protein with mice antisera was validated by SPR analysis. These results suggest that Fu and bc epitope-based recombinant fusion protein could be a potential candidate towards the development of the effective subunit vaccine against DENV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10541-y) contains supplementary material, which is available to authorized users.


id: cord-011026-iapgkz0p
author: El-Bitar, Alaa M. H.
date: 2019-07-06
txt: ./txt/cord-011026-iapgkz0p.txt
cache: ./cache/cord-011026-iapgkz0p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223391/
doi: 10.1007/s10989-019-09888-2
summary:
  title: Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). For dengue virus infectivity, serially diluted venom fractions and Smp76 were mixed with fixed amount of DENV and incubated for 2 h at 37 °C. The above results suggest that the Smp76 directly affects HCV particles and/or host cells in the culture medium to inhibit the viral infection and does not have an antiviral effect in the cells. To determine whether the antiviral activity of Smp76 peptide (previously described) was specific to HCV and DENV, a Schematic of infection assay. The exact mechanism by which Smp76 exerts its antiviral activity against HCV and DENV to inhibit infecting their target cells need further studies.

title:
  Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus

abstract:
  Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC(50) of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses.


id: cord-011390-98xyie7s
title: Multiple arboviral infections during a DENV-2 outbreak in Solomon Islands
author: Darcy, Andrew Waleluma
date: 2020-05-15
txt: ./txt/cord-011390-98xyie7s.txt
cache: ./cache/cord-011390-98xyie7s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225641/
doi: 10.1186/s41182-020-00217-8
summary:
  An outbreak of dengue-like illness (DLI) that occurred in April 2016 prompted this study, which aimed to determine the population''s immunity status and identify the arboviruses circulating in the country. The study objectives were to estimate the seroprevalence of arboviruses in the urban population of Solomon Islands while using qPCR to determine the circulating viruses from the clinical samples; furthermore, to characterize and compare the dengue virus isolated from our study to previous published isolates from the region using the phylogenetic tree analysis. The high positivity rate for anti-DENV IgG antibodies (77.9%) and the high DENV positivity rate detected in the qPCR analysis of the clinical samples (76.3%) were indicative of a high number of secondary infections in the 2016 outbreak. The phylogenetic tree analysis and the serotypespecific qPCR results indicated that there was a single DENV-3 serotype in circulation from 2012 to 2016 in Solomon Islands.

abstract:
  BACKGROUND: Solomon Islands, a country made up of tropical islands, has suffered cyclic dengue fever (DF) outbreaks in the past three decades. An outbreak of dengue-like illness (DLI) that occurred in April 2016 prompted this study, which aimed to determine the population’s immunity status and identify the arboviruses circulating in the country. METHODS: A household survey, involving 188 participants in two urban areas (Honiara and Gizo), and a parallel hospital-based clinical survey were conducted in April 2016. The latter was repeated in December after a surge in DLI cases. Arbovirus IgG ELISA were performed on the household blood samples to determine the prevalence of arboviruses in the community, while qPCR testing of the clinical samples was used to identify the circulating arboviruses. Dengue virus (DENV)-positive samples were further characterized by amplifying and sequencing the envelope gene. RESULTS: The overall prevalence rates of DENV, Zika virus, and chikungunya virus were 83.4%, 7.6%, and 0.9%, respectively. The qPCR positivity rates of the clinical samples collected in April 2016 were as follows: DENV 39.6%, Zika virus 16.7%, and chikungunya virus 6.3%, which increased to 74%, 48%, and 20% respectively in December 2016. The displacement of the circulating serotype-3, genotype-1, with DENV serotype 2, genotype cosmopolitan was responsible for the outbreak in 2016. CONCLUSIONS: A DENV outbreak in Solomon Islands was caused by the introduction of a single serotype. The high prevalence of DENV provided transient cross-protection, which prevented the introduction of a new serotype from the hyperendemic region for at least 3 years. The severe outcomes seen in the recent outbreak probably resulted from changes in the causative viruses and the effects of population immunity and changes in the outbreak pattern. Solomon Islands needs to step up surveillance to include molecular tools, increase regional communication, and perform timely interventions.


id: cord-011968-abd891ej
author: Lai, Yen-Chung
date: 2020-06-12
txt: ./txt/cord-011968-abd891ej.txt
cache: ./cache/cord-011968-abd891ej.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356240/
doi: 10.3390/microorganisms8060891
summary:
  Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that mediates diverse immune responses, and the serum level of MIF positively correlates with disease severity in patients with dengue. In another study, it was demonstrated that live DENV2-induced endoplasmic reticulum (ER) stress is required for autophagy activation, viral replication and pathogenesis in HuH-7 and A549 cells [57] . In our study, since UV-inactivated viral particles could not induce MIF secretion or expression, it is possible that DENV infection triggered RNA sensing or pattern recognition receptor (PRR) activation, which was followed by the release of preformed MIF from the cytosol through the vesicle trafficking secretory pathway. Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability Minocycline suppresses dengue virus replication by down-regulation of macrophage migration inhibitory factor-induced autophagy Dengue virus nonstructural protein 1 induces vascular leakage through macrophage migration inhibitory factor and autophagy

title:
  Roles of Macrophage Migration Inhibitory Factor in Dengue Pathogenesis: From Pathogenic Factor to Therapeutic Target

abstract:
  Dengue virus (DENV) infection is the most prevalent mosquito-borne viral infection and can lead to severe dengue hemorrhagic fever (DHF) and even life-threatening dengue shock syndrome (DSS). Although the cytokine storm has been revealed as a critical factor in dengue disease, the limited understanding of dengue immunopathogenesis hinders the development of effective treatments. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that mediates diverse immune responses, and the serum level of MIF positively correlates with disease severity in patients with dengue. MIF is involved in DENV replication and many pathological changes, such as vascular leakage, during DENV infection. In this paper, the pathogenic roles of MIF and the regulation of MIF secretion during DENV infection are reviewed. Furthermore, whether MIF is a potential therapeutic target against DENV infection is also discussed.


id: cord-025181-eg108wcd
author: Zheng, Zhihang
date: 2020-05-25
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246292/
doi: 10.1007/s12250-020-00229-y
title:
  Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate

abstract:
  Dengue virus (DENV) is a single-stranded RNA virus transmitted by mosquitoes in tropical and subtropical regions. It causes dengue fever, dengue hemorrhagic fever and dengue shock syndrome in patients. Each year, 390 million people are estimated to be infected by four serotypes of dengue virus, creating a great burden on global public health and local economy. So far, no antiviral drug is available for dengue disease, and the newly licensed vaccine is far from satisfactory. One large obstacle for dengue vaccine and drug development is the lack of suitable small animal models. Although some DENV infection models have been developed, only a small number of viral strains can infect immunodeficient mice. In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. This study not only offers new small animal models of dengue viral infection, but also provides new viral variants for further investigations on dengue viral pathogenesis.


id: cord-033331-giku34r9
author: Manrique-Saide, Pablo
date: 2020-10-08
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542575/
doi: 10.1186/s13063-020-04780-7
title:
  The TIRS trial: protocol for a cluster randomized controlled trial assessing the efficacy of preventive targeted indoor residual spraying to reduce Aedes-borne viral illnesses in Merida, Mexico

abstract:
  BACKGROUND: Current urban vector control strategies have failed to contain dengue epidemics and to prevent the global expansion of Aedes-borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the paucity of evidence regarding the epidemiological impact of any Aedes control method. A strategy for which there is limited epidemiological evidence is targeted indoor residual spraying (TIRS). TIRS is a modification of classic malaria indoor residual spraying that accounts for Aedes aegypti resting behavior by applying residual insecticides on exposed lower sections of walls (< 1.5 m), under furniture, and on dark surfaces. METHODS/DESIGN: We are pursuing a two-arm, parallel, unblinded, cluster randomized controlled trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory-confirmed ABV clinical disease (primary endpoint). The trial will be conducted in the city of Merida, Yucatan State, Mexico (population ~ 1million), where we will prospectively follow 4600 children aged 2–15 years at enrollment, distributed in 50 clusters of 5 × 5 city blocks each. Clusters will be randomly allocated (n = 25 per arm) using covariate-constrained randomization. A “fried egg” design will be followed, in which all blocks of the 5 × 5 cluster receive the intervention, but all sampling to evaluate the epidemiological and entomological endpoints will occur in the “yolk,” the center 3 × 3 city blocks of each cluster. TIRS will be implemented as a preventive application (~ 1–2 months prior to the beginning of the ABV season). Active monitoring for symptomatic ABV illness will occur through weekly household visits and enhanced surveillance. Annual sero-surveys will be performed after each transmission season and entomological evaluations of Ae. aegypti indoor abundance and ABV infection rates monthly during the period of active surveillance. Epidemiological and entomological evaluation will continue for up to three transmission seasons. DISCUSSION: The findings from this study will provide robust epidemiological evidence of the efficacy of TIRS in reducing ABV illness and infection. If efficacious, TIRS could drive a paradigm shift in Aedes control by considering Ae. aegypti behavior to guide residual insecticide applications and changing deployment to preemptive control (rather than in response to symptomatic cases), two major enhancements to existing practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343521. Registered on 13 April 2020. The protocol also complies with the WHO International Clinical Trials Registry Platform (ICTRP) (Additional file 1). PRIMARY SPONSOR: National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID).


id: cord-253480-qchrw337
title: Antiviral activity of Carbenoxolone disodium against dengue virus infection
author: Pu, Jieying
date: 2016-12-23
txt: ./txt/cord-253480-qchrw337.txt
cache: ./cache/cord-253480-qchrw337.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27155198/
doi: 10.1002/jmv.24571
summary:
  Here, we found that the production of infectious DENV particles was significantly decreased by CBX treatment in DENV‐permissive cells, while the viral RNA and viral protein synthesis were not affected. Moreover, results from time-of-addition study showed that the inhibitory effect of CBX on DENV was exhibited by targeting the virus itself, not the host cells. In this study, we investigated whether CBX treatment inhibits dengue infection by measuring the production of progeny virions and viral RNA as well as viral protein expression. To determine whether CBX inhibits the production of infectious progeny DENV in other dengue-permissive cells, TCID 50 assay was performed to measure the virus titer in CBX-treated THP-1 and HUVEC cells, both of which are widely used in DENV studies [Halstead, 1988; Wu et al., 2000] . CBX treatment did not inhibit DENV-1 or DENV-2 RNA synthesis and protein expression in one replication cycle, but markedly reduced progeny virus The total RNA was isolated from the infected cells and analyzed by quantitative RT-PCR.

abstract:
  As one of the most important mosquito‐borne viral diseases, dengue infection is now becoming a global concern due to its rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus (DENV) infection. Glycyrrhetinic acid (GNa) and its related derivatives have been reported to inhibit a broad spectrum of viruses. However, it is unknown whether Carbenoxolone disodium (CBX), one of the GNa derivatives, affects DENV infection. Here, we found that the production of infectious DENV particles was significantly decreased by CBX treatment in DENV‐permissive cells, while the viral RNA and viral protein synthesis were not affected. Moreover, results from time‐of‐addition study showed that the inhibitory effect of CBX on DENV was exhibited by targeting the virus itself, not the host cells. Directly incubating DENV with CBX resulted in a remarkable reduction of virus titer and virus infectivity. Furthermore, DENV RNA from progeny virions in the supernatants was significantly decreased by CBX treatment in a dose‐dependent manner. Taken together, these data indicate that the antiviral activity of CBX against DENV may be mainly due to a virucidal effect exerted by the compound itself. Our work, for the first time, demonstrates that CBX has antiviral activity against DENV infection, providing useful information for development of potential therapeutic interventions against dengue. J. Med. Virol. 89:571–581, 2017. © 2016 Wiley Periodicals, Inc.


id: cord-256732-md1u51va
title: Inflammasome Fuels Dengue Severity
author: Shrivastava, Gaurav
date: 2020-09-10
txt: ./txt/cord-256732-md1u51va.txt
cache: ./cache/cord-256732-md1u51va.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33014899/
doi: 10.3389/fcimb.2020.00489
summary:
  Inflammasome plays a vital function in the host innate immune system by regulating the secretion of proinflammatory cytokines (IL-1β and IL-18) and subsequent induction of "pyroptosis, " a form of programmed cell death, activated by inflammatory caspases (Fink and Cookson, 2006; Lamkanfi and Dixit, 2014) . IL-1β secretion further enhances the production and release of IL-23 and IL-6 and the association of IL-18, IL-1β, and IL-23 stimulate Th17/γδ T cells to generate pro-inflammatory cytokines (GM-CSF, IL-17A, IL-17F, IL-22,) that create the stage for host adaptive immune responses during DENV infection (Wu et al., 2013a) . Another study demonstrated that DENV infects DC and induces NLRP3 inflammasome activation, triggering ROS production in mitochondria that leads to the discharge of mitochondrial DNA (mtDNA) into the cytosol. (D) DENV activates platelets and induces the secretion of EVs (DV-EXOs and DV-MVs), that results in the CLEC5A and TLR2 mediated release of proinflammatory cytokines and NETs formation in neutrophils contributing to vascular leakage during dengue infection.

abstract:
  Dengue is an acute febrile disease triggered by dengue virus. Dengue is the widespread and rapidly transmitted mosquito-borne viral disease of humans. Diverse symptoms and diseases due to Dengue virus (DENV) infection ranges from dengue fever, dengue hemorrhagic fever (life-threatening) and dengue shock syndrome characterized by shock, endothelial dysfunction and vascular leakage. Several studies have linked the severity of dengue with the induction of inflammasome. DENV activates the NLRP3-specific inflammasome in DENV infected human patients, mice; specifically, mouse bone marrow derived macrophages (BMDMs), dendritic cells, endothelial cells, human peripheral blood mononuclear cells (PBMCs), keratinocytes, monocyte-differentiated macrophages (THP-1), and platelets. Dengue virus mediated inflammasome initiates the maturation of IL-1β and IL-18, which are critical for dengue pathology and inflammatory response. Several studies have reported the molecular mechanism through which (host and viral factors) dengue induces inflammasome, unravels the possible mechanisms of DENV pathogenesis and sets up the stage for the advancement of DENV therapeutics. In this perspective article, we discuss the potential implications and our understanding of inflammasome mechanisms of dengue virus and highlight research areas that have potential to inhibit the pathogenesis of viral diseases, specifically for dengue.


id: cord-270495-2u072mtp
title: Diagnosis of COVID-19 in a Dengue-Endemic Area
author: Lokida, Dewi
date: 2020-08-05
txt: ./txt/cord-270495-2u072mtp.txt
cache: ./cache/cord-270495-2u072mtp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32762798/
doi: 10.4269/ajtmh.20-0676
summary:
  When SARS-CoV-2 is negative and clinical indication is present (at least fever and thrombocytopenia), DENV NS1 antigen and/or IgM/IgG antibody testing may be performed. Clinicians from Singapore reported two COVID-19 cases that were misdiagnosed as dengue among patients who presented with clinical manifestations and hematology profiles, suggesting dengue infection and false-positive DENV IgM antibody using a rapid diagnostic test (RDT). COVID-19 cases were defined as inpatients who met the COVID-19 criteria based on a predetermined combination of symptoms, laboratory testing, imaging, and risk exposure at Tangerang District Hospital, Indonesia (see Supplemental Table 1 ), and had a positive nasopharyngeal or oropharyngeal real-time RT-PCR for SARS-CoV-2. None of the 42 subjects was positive for dengue NS1 or showed seroconversion or increasing DENV IgM and IgG index values, suggesting no acute DENV infection among these COVID-19 cases. The third patient did not recall having a fever before acute COVID-19 illness, suggesting asymptomatic or mild dengue, the most common presentation of DENV infection.

abstract:
  Emergence of SARS-CoV-2 in dengue virus (DENV)–endemic areas complicates the diagnosis of both infections. COVID-19 cases may be misdiagnosed as dengue, particularly when relying on DENV IgM, which can remain positive months after infection. To estimate the extent of this problem, we evaluated sera from 42 confirmed COVID-19 patients for evidence of DENV infection. No cases of SARS-CoV-2 and DENV coinfection were identified. However, recent DENV infection, indicated by the presence of DENV IgM and/or high level of IgG antibodies, was found in seven patients. Dengue virus IgM and/or high IgG titer should not exclude COVID-19. SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing is appropriate when dengue nonstructural protein 1 (NS1) or RT-PCR is negative. Given the possibility of coinfection, testing for both DENV and SARS-CoV-2 is merited in the setting of the current pandemic.


id: cord-272459-w14finxf
title: Dengue Virus and Autophagy
author: Heaton, Nicholas S.
date: 2011-08-04
txt: ./txt/cord-272459-w14finxf.txt
cache: ./cache/cord-272459-w14finxf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21994782/
doi: 10.3390/v3081332
summary:
  Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. Relevant to DENV infection, a type of selective autophagy termed lipophagy was described, wherein autophagosomes can target cellular stores of lipids known as lipid droplets (LDs) to generate energy for the cell [38] . In subsequent work, the authors reproduced the published results that DENV induces and requires autophagy for robust viral replication [39] . These autophagosomes did not co-localize with markers of the viral replication complex, suggesting that they may play an indirect, non-structural role in DENV replication. Alternatively, DENV infection induces a selective autophagy that is preferentially targeted to lipid droplets, which leads to changes in cellular metabolism. More work, however, is required to show whether the proposed viral triggers of autophagy reproduce all cellular signals and phenotypes that accompany autophagy induction in DENV-infected cells.

abstract:
  Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER) cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.


id: cord-273065-peqz7okh
title: Arboviruses: A global public health threat
author: Girard, Marc
date: 2020-04-24
url: https://www.sciencedirect.com/science/article/pii/S0264410X20304709
doi: 10.1016/j.vaccine.2020.04.011
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.


id: cord-273388-615acz0l
title: The Impact of Emerging Infectious Diseases on Chinese Blood Safety()
author: He, Miao
date: 2016-11-04
url: https://www.ncbi.nlm.nih.gov/pubmed/27923518/
doi: 10.1016/j.tmrv.2016.10.002
abstract:
  Emerging infectious diseases (EIDs) have always been one of the major threats to public health. Although the implementation of mandatory testing for 4 classical transfusion-transmitted infectious—human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis—has reduced the transfusion risk of these pathogens, the potential threat of various EID agents and their constantly evolving variants to blood safety in China is not fully understood. This review presents 9 representative EID agents that are autochthonous and epidemic nationally or regionally in China. The epidemiologic status and distribution of these EID agents among donors and/or healthy populations are summarized. The potential risks of these EID agents to blood safety are discussed. The review also explores strategies to strengthen hemovigilance systems and studies to further evaluate the impact of EID agents on blood safety.


id: cord-274129-vaygaqe5
author: Cheng, Ming Soon
date: 2015-08-15
url: https://doi.org/10.1016/j.bios.2015.03.018
doi: 10.1016/j.bios.2015.03.018
title:
  Impedimetric cell-based biosensor for real-time monitoring of cytopathic effects induced by dengue viruses

abstract:
  We describe an impedimetric cell-based biosensor constructed from poly-l-lysine (PLL)-modified screen-printed carbon electrode for real-time monitoring of dengue virus (DENV) infection of surface-immobilized baby hamster kidney (BHK-21) fibroblast cells. Cytopathic effects (CPE) induced by DENV-2 New Guinea C strain (including degenerative morphological changes, detachment, membrane degradation and death of host cells), were reflected by drastic decrease in impedance signal response detected as early as ~30 hours post-infection (hpi). In contrast, distinct CPE by conventional microscopy was evident only at ~72 hpi at the corresponding multiplicity of infection (MOI) of 10. A parameter that describes the kinetics of cytopathogenesis, CIT(50), which refers to the time taken for 50% reduction in impedance signal response, revealed an inverse linear relationship with virus titer and MOI. CIT(50) values were also delayed by 31.5 h for each order of magnitude decrease in MOI. Therefore, based on the analysis of CIT(50), the virus titer of a given sample can be determined from the measured impedance signal response. Furthermore, consistent impedance results were also obtained with clinical isolates of the four DENV serotypes verified by RT-PCR and cycle sequencing. This impedimetric cell-based biosensor represents a label-free and continuous approach for the dynamic measurement of cellular responses toward DENV infection, and for detecting the presence of infectious viral particles.


id: cord-276364-zyw5aukk
title: Manipulation of autophagy by (+) RNA viruses
author: Wong, Ho Him
date: 2019-08-08
txt: ./txt/cord-276364-zyw5aukk.txt
cache: ./cache/cord-276364-zyw5aukk.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1084952118302222
doi: 10.1016/j.semcdb.2019.07.013
summary:
  Over the past few decades, a growing body of research has defined the critical role of this pathway in facilitating infection by numerous +RNA RNA viruses, including poliovirus (PV) [7, 8] , Coxsackievirus B3 (CVB3) [9, 10] , CVB4 [11] , Enterovirus 71 (EV71) [12] , Human rhinovirus (HRV) [13] , Foot-and-mouth disease virus (FMDV) [14] , encephalomyocarditis virus (EMCV) [15] , Dengue virus (DENV) [16, 17] , Zika virus (ZIKV) [18, 19] , Hepatitis C virus (HCV) [20] , Mouse hepatitic virus (MHV), Newcastle disease virus (NDV) [21] , Severe and acute respiratory syndrome coronavirus (SARS-CoV) [22] , Chikungunya virus (ChikV) [23] , and Japanese encephalitis virus (JEV) [24] . Delineating the process of viral assembly from replication is technically challenging, especially since both processes would very likely Induces formation of autophagosome-like double-membrane liposomes [112] Summary of Interactions between proteins from positive strand RNA viruses and host autophagy machinery.

abstract:
  Autophagy is an evolutionarily conserved process central to host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention.


id: cord-276718-3lujp0oy
author: Neeraja, M.
date: 2014-10-24
txt: ./txt/cord-276718-3lujp0oy.txt
cache: ./cache/cord-276718-3lujp0oy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25455901/
doi: 10.1016/j.jviromet.2014.10.005
summary:
  title: Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Hyderabad, India In the present study, the standardization and validation of a one step, four tube reverse transcription loop-mediated isothermal amplification assay (RT-LAMP) for rapid detection and serotyping of the DENV targeting NS1 gene using the Genie® II flourometer was carried out. In the present study, the RT-LAMP assay was developed for the detection and serotyping of DENV infection targeting the serotype specific regions of the NS1 gene using a real-time flourometer (Genie ® II from Optigene, U.K.). The performance of the RT-LAMP assay was validated by testing the samples simultaneously by the CDC real time PCR that is most sensitive and specific method for detection and differentiation of the DENV (CDC Dengue). Rapid detection and differentiation of dengue virus serotypes by a real-time reverse transcription-loop-mediated isothermal amplification assay

title:
  Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Hyderabad, India

abstract:
  Early and rapid detection of dengue virus (DENV) infection during the acute phase of illness is crucial for proper patient management and prevention of the spread of the infection. In the present study, the standardization and validation of a one step, four tube reverse transcription loop-mediated isothermal amplification assay (RT-LAMP) for rapid detection and serotyping of the DENV targeting NS1 gene using the Genie® II flourometer was carried out. The performance of the RT-LAMP was compared to RT-PCR, CDC 1-4 Real time PCR and the NS1 antigen ELISA, IgM and IgG anti DENV antibodies. Acute DENV infection was confirmed in 250/300 patients suspected clinically of DENV infection. RT- LAMP and CDC 1-4 Real time PCR assay was positive in 148/250 patients, while 92/250 patients were positive for anti- Dengue IgM and IgG antibodies. The RT-LAMP assay and the CDC real-time RT-PCR assay showed high concordance (k = 1.0). The detection rate of acute DENV infection improved to 96% (240/250) when the results of RT-LAMP were combined with NS1 Ag, IgM and IgG ELISA. The RT-LAMP had a detection limit of 100 copies for DEN-1 and DEN-2, 10 copies for DEN-3 and DEN-4 compared to 1000 copies for DEN-1 and DEN-2, 100 copies for DEN-3 and DEN-4 by the conventional RT-PCR. The assay showed 100% specificity. The RT-LAMP assay developed in this study has potential use for early clinical diagnosis, serotyping and surveillance of DENV infection in endemic countries such as India.


id: cord-277547-2vim1wno
title: Antiviral activity of four types of bioflavonoid against dengue virus type-2
author: Zandi, Keivan
date: 2011-12-28
txt: ./txt/cord-277547-2vim1wno.txt
cache: ./cache/cord-277547-2vim1wno.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22201648/
doi: 10.1186/1743-422x-8-560
summary:
  In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Daidzein showed a weak anti-dengue activity with IC(50 )= 142.6 μg mL(-1 )when the DENV-2 infected cells were treated after virus adsorption. Although there was no significant direct virucidal activity against DENV-2 by quercetin, continuous treatment of cells from 5 h before virus infection up to 4 days post-infection exhibited anti-dengue activity with IC 50 = 28.9 μg mL -1 (Figure 3a) . There was no significant change in the antiviral activity of daidzein when cells were treated continuously from 5 h before virus infection up to 4 days post infection comparing to its anti-dengue activity for postadsorption treatment (Figure 1 ). To investigate which of the many flavonoids could affect DENV infection, in the present study, we examined the potential effects of quercetin, naringin, hesperetin and daidzein on dengue virus infection of Vero cells.

abstract:
  BACKGROUND: Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC(50)) to inhibitory concentration 50 (IC(50)) for each compound. RESULTS: The half maximal inhibitory concentration (IC(50)) of quercetin against dengue virus was 35.7 μg mL(-1 )when it was used after virus adsorption to the cells. The IC(50 )decreased to 28.9 μg mL(-1 )when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL(-1), respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC(50 )= 168.2 μg mL(-1 )and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC(50 )= 142.6 μg mL(-1 )when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL(-1)) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. CONCLUSION: Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids, including daidzein, naringin and hesperetin showed minimal to no significant inhibition of DENV-2 virus replication. These findings, together with those previously reported suggest that select group of bioflavonoids including quercetin and fisetin, exhibited significant inhibitory activities against dengue virus. This group of flavonoids, flavonol, could be investigated further to discover the common mechanisms of inhibition of dengue virus replication.


id: cord-278260-3o91v72a
title: COVID 19 Vaccines: Should we fear ADE?
author: Halstead, Scott B
date: 2020-08-12
txt: ./txt/cord-278260-3o91v72a.txt
cache: ./cache/cord-278260-3o91v72a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32785649/
doi: 10.1093/infdis/jiaa518
summary:
  Within months large numbers of vaccinated children developed a severe breakthrough disease, called "atypical measles." [6] A similar outcome, "vaccine associated enhanced respiratory disease (VAERD)," was observed in infants, 4 -12 months of age, who were given formalininactivated respiratory syncytial virus (RSV) and a few months later infected by RSV. The biological behavior of some coronaviruses in non-human species together with evidence that human coronavirus antibodies enhanced infection of SARS or MERS CoVs in Fc receptor-bearing cells, in vitro, have led to speculations that ADE contributes to disease severity in humans. [11] It has been reported that high levels of SARS CoV-1 IgG antibodies circulated in severe SARS cases and that anti-S IgG neutralizing antibody (NAb) responses developed significantly faster after the onset of clinical symptoms in fatal compared with recovered cases leading some to attribute enhanced tissue damage to ADE. With others, we conclude that the differences in clinical, epidemiological and pathological features of SARS and DENV diseases suggest that iADE does not contribute to the severity of natural human coronavirus infections.

abstract:
  Might COVID 19 vaccines sensitize humans to antibody dependent enhanced (ADE) breakthrough infections? This outcome is unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological or pathological attributes of ADE disease exemplified by the dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantly infect respiratory epithelium, not macrophages. Severe disease centers on older persons with pre-existing conditions and not young infants or individuals with previous coronavirus infections. Live virus challenge of animals given SARS or MERS vaccines has resulted in vaccine hypersensitivity reactions (VAH), similar to those in humans given inactivated measles or respiratory syncytial virus vaccines. Safe and effective COVID 19 vaccines must avoid VAH.


id: cord-282204-j1slaefb
author: Silva, José V.J.
date: 2018-12-31
txt: ./txt/cord-282204-j1slaefb.txt
cache: ./cache/cord-282204-j1slaefb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.actatropica.2018.09.003
doi: 10.1016/j.actatropica.2018.09.003
summary:
  de; Oliveira, Renato A.S.; Durães-Carvalho, Ricardo; Lopes, Thaísa R.R.; Silva, Daisy E.A.; Gil, Laura H.V.G. title: A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control Laboratory tests for specific diagnosis of CHIKV infection are based on virus isolation, viral RNA detection and serology (Johnson et al., 2016) . Anti-CHIKV candidates that have been already tested in humans and/or animals include inactivated-, attenuated-, virus like particle-(VLP), DNA-and chimeric vaccines (Eckels et al., 1970; Levitt et al., 1986; Muthumani et al., 2008; Wang et al., 2008; Tiwari et al., 2009; Sharma et al., 2012 Akahata et al., 2010 Plante et al., 2011; Wang et al., 2011; Gorchakov et al., 2012; Brandler et al., 2013; Chang et al., 2014; García-Arriaza et al., 2014; Tretyakova et al., 2014; van den Doel et al., 2014; Erasmus et al., 2017) .

title:
  A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control

abstract:
  Abstract Chikungunya fever is a mosquito-borne viral illness characterized by a sudden onset of fever associated with joint pains. It was first described in the 1950s during a Chikungunya virus (CHIKV) outbreak in southern Tanzania and has since (re-) emerged and spread to several other geographical areas, reaching large populations and causing massive epidemics. In recent years, CHIKV has gained considerable attention due to its quick spread to the Caribbean and then in the Americas, with many cases reported between 2014 and 2017. CHIKV has further garnered attention due to the clinical diagnostic difficulties when Zika (ZIKV) and dengue (DENV) viruses are simultaneously present. In this review, topical CHIKV-related issues, such as epidemiology and transmission, are examined. The different manifestations of infection (acute, chronic and atypical) are described and a particular focus is placed upon the diagnostic handling in the case of ZIKV and DENV co-circulating. Natural and synthetic compounds under evaluation for treatment of chikungunya disease, including drugs already licensed for other purposes, are also discussed. Finally, previous and current vaccine strategies, as well as the control of the CHIKV transmission through an integrated vector management, are reviewed in some detail.


id: cord-282742-eyukbot7
title: Arthropod-Borne Flaviviruses and RNA Interference: Seeking New Approaches for Antiviral Therapy
author: Diosa-Toro, Mayra
date: 2013-02-20
txt: ./txt/cord-282742-eyukbot7.txt
cache: ./cache/cord-282742-eyukbot7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780124081161000045
doi: 10.1016/b978-0-12-408116-1.00004-5
summary:
  Geiss, Pierson, and Diamond (2005) observed that siRNAs targeting the C gene had no effect on virus replication when transfected into cells 10 h after WNV infection using lipid-based reagents. In addition, no significant reduction in viral protein or RNA levels was seen in WNV replicon-expressing cells transfected with siRNAs targeting the NS3 gene using lipid-based reagents. Also, a recent report showed that siRNA toward the TNF-a gene reduced cytokine response in DENV-infected DCs, highlighting the potential of targeted RNAi-based approaches to simultaneously decrease viral replication and the detrimental host immune response (Subramanya et al., 2010) . In addition, it has been shown that WNV (Chotkowski et al., 2008) and DENV (Mukherjee & Hanley, 2010) infection (Mukherjee & Hanley, 2010) of Drosophila cell lines induce functional virus-specific siRNAs that promote a protective RNAi response. So far we have described the antiviral effect of the RNAi mechanism induced by exogenous delivery of siRNA or precursors, and how cellular miRNA can target sequences artificially introduced within the genome of flaviviruses.

abstract:
  Flaviviruses are the most prevalent arthropod-borne viruses worldwide, and nearly half of the 70 Flavivirus members identified are human pathogens. Despite the huge clinical impact of flaviviruses, there is no specific human antiviral therapy available to treat infection with any of the flaviviruses. Therefore, there is a continued search for novel therapies, and this review describes the current knowledge on the usage of RNA interference (RNAi) in combating flavivirus infections. RNAi is a process of sequence-specific gene silencing triggered by double-stranded RNA. Antiviral RNAi strategies against arthropod-borne flaviviruses have been reported and although several hurdles must be overcome to employ this technology in clinical applications, they potentially represent a new therapeutic tool.


id: cord-285538-3ah05ijf
title: Chapter 19 Pathogenic Exploitation of Fc Activity
author: Halstead, Scott B.
date: 2014-12-31
txt: ./txt/cord-285538-3ah05ijf.txt
cache: ./cache/cord-285538-3ah05ijf.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780123948021000194
doi: 10.1016/b978-0-12-394802-1.00019-4
summary:
  3, 4 While follow-up research in the 1960s suggested that this phenomenon resulted from the stabilization of MVEV by antibodies, 5 a different explanation emerged when sequential infections in humans with dengue viruses (DENVs) were shown to produce severe disease (dengue hemorrhagic fever, DHF). Unexpectedly, the incubation of Ross River virus (RRV) with diluted RRV antiserum resulted in enhanced infection in mouse macrophage cell lines and in primary human monocytes/macrophages via innate immune suppression involving reduced production of reactive nitrogen radicals via NOS2 and a downregulation of TNF-α and IFN-β production through abolished interferon regulatory factor 1 (IRF-1) and nuclear factor-κB gene expression. 43 Note has been made above of the possible role of different Fcγ receptors in mediating ADE in macrophages in leishmania mouse models and the interesting observation suggesting that ligation of FcγRIIB may affect the fate of large immune complexes during the immune clearance phase of dengue infections.

abstract:
  While the benefits of antibody responses are widely known, pathogens are also able to exploit antibodies to facilitate cell entry and potentially alter the cellular response via interactions with Fc receptors. This phenomenon, known as antibody-dependent enhancement (ADE) of disease, is a factor in numerous human and veterinary diseases. It is thought to result from innate cellular responses to Fcγ receptor-facilitated entry of infectious microbial immune complexes, and paradoxically results in increased production of pathogenic organisms. ADE has been described in vitro in numerous settings, but the strongest data regarding the in vivo impact of this mechanism on human disease come from human disease and animal models of dengue and leishmanial infections. This chapter reviews the literature of ADE in relation to the innate immune responses to Fcγ receptor ligation by infectious IgG immune complexes and discusses the research frontiers regarding this harmful antibody activity.


id: cord-286255-ded5t1ai
author: Tomashek, Kay M.
date: 2017-09-13
txt: ./txt/cord-286255-ded5t1ai.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28902845/
doi: 10.1371/journal.pntd.0005859
summary:
  Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. Among 6,349 participants who presented early (<3 DPO) in the clinical course, leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness were significant positive predictors of laboratory-positive dengue as compared to all other AFI cases across all age groups ( Table 5 ). Of note, 6% of participants !65 years old had dengue as a cause of AFI, a finding comparable to a Puerto Rico study in which 5% of 17,666 laboratory-positive dengue cases detected by surveillance were !65 years old [36] .

title:
  Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012–2015

abstract:
  Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1–4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3–5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.


id: cord-290385-0smnl70i
title: Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease
author: Chan, Jasper F.W.
date: 2016-03-03
url: https://www.sciencedirect.com/science/article/pii/S016344531600061X
doi: 10.1016/j.jinf.2016.02.011
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.


id: cord-294842-aesiff1f
title: Membranous Replication Factories Induced by Plus-Strand RNA Viruses
author: Romero-Brey, Inés
date: 2014-07-22
url: https://doi.org/10.3390/v6072826
doi: 10.3390/v6072826
abstract:
  In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments.


id: cord-295191-xu26mvc3
title: Complement and its role in protection and pathogenesis of flavivirus infections
author: Avirutnan, Panisadee
date: 2008-12-30
url: https://www.sciencedirect.com/science/article/pii/S0264410X08016083
doi: 10.1016/j.vaccine.2008.11.061
abstract:
  The complement system is a family of serum and cell surface proteins that recognize pathogen-associated molecular patterns, altered-self ligands, and immune complexes. Activation of the complement cascade triggers several antiviral functions including pathogen opsonization and/or lysis, and priming of adaptive immune responses. In this review, we will examine the role of complement activation in protection and/or pathogenesis against infection by Flaviviruses, with an emphasis on experiments with West Nile and Dengue viruses.


id: cord-297662-slmlhqnb
title: Dengue Virus Glycosylation: What Do We Know?
author: Yap, Sally S. L.
date: 2017-07-25
txt: ./txt/cord-297662-slmlhqnb.txt
cache: ./cache/cord-297662-slmlhqnb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2017.01415
doi: 10.3389/fmicb.2017.01415
summary:
  In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis. Since high mannose binding DC-SIGN interacts only with N67 glycans on the viral surface (Pokidysheva et al., 2006) and N153-glycan is dispensable for virus production in mosquito and mammalian cells (Bryant et al., 2007) , this suggests that N153 glycans may serve a distinct function from N67 glycans in DEN pathogenesis possibly via interaction with an unknown fucose binder or act as a viral glycan shield. Finally, N153 deglycosylated (N153 − ) DENV mutant displayed reduced infectivity (10-fold lower) in both mammalian and mosquito cells compared to WT, possibly due to impaired virus entry process (Lee et al., 1997; Hacker et al., 2009) , whereby loss of the N153-glycan affected the conformational stability of E proteins and led to premature exposure of the fusion peptide (Yoshii et al., 2013) . N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement

abstract:
  In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E) and non-structural protein 1 (NS1) are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.


id: cord-300648-ixiam7qr
title: IFITM3‐containing exosome as a novel mediator for anti‐viral response in dengue virus infection
author: Zhu, Xun
date: 2014-08-30
url: https://www.ncbi.nlm.nih.gov/pubmed/25131332/
doi: 10.1111/cmi.12339
abstract:
  Interferon‐inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV‐2 infection, we found that IFITM3 contributed to both the baseline and interferon‐induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM‐containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non‐infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome‐mediated anti‐viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species.


id: cord-303818-z3js3mr4
author: Chen, Huixin
date: 2015-10-11
url: https://www.sciencedirect.com/science/article/pii/S1525157815001567
doi: 10.1016/j.jmoldx.2015.06.008
title:
  Development and Evaluation of a SYBR Green–Based Real-Time Multiplex RT-PCR Assay for Simultaneous Detection and Serotyping of Dengue and Chikungunya Viruses

abstract:
  Chikungunya virus (CHIKV) and dengue virus (DENV) have emerged as the two most important arbovirus diseases of global health significance. Similar clinical manifestations, transmission vectors, geographical distribution, and seasonal correlation often result in misdiagnosis of chikungunya infections as dengue cases and vice versa. In this study, we developed a rapid and accurate laboratory confirmative method to simultaneously detect, quantify, and differentiate DENV serotypes 1, 2, 3, and 4 and CHIKV. This SYBR Green I–based one-step multiplex real-time RT-PCR assay is highly sensitive and specific for CHIKV and DENV. Melting temperature analysis of PCR amplicons was used to serotype DENV and to differentiate from CHIKV. The detection limit of the assay was 20, 10, 50, 5, and 10 RNA copies/reaction for DENV-1, DENV-2, DENV-3, DENV-4, and CHIKV, respectively. Our assay did not cross-react with a panel of viruses that included other flaviviruses, alphaviruses, influenza viruses, human enteroviruses, and human coronaviruses. The feasibility of using this assay for clinical diagnosis was evaluated in DENV- and CHIKV-positive patient sera. Accordingly, the assay sensitivity for DENV-1, DENV-2, DENV-3, DENV-4, and CHIKV was 89.66%, 96.67%, 96.67%, 94.12%, and 95.74%, respectively, with 100% specificity. These findings confirmed the potential of our assay to be used as a rapid test for simultaneous detection and serotyping of DENV and CHIKV in clinical samples.


id: cord-306204-rkher4ly
title: Anti-dengue virus serotype 2 activity of tannins from porcupine dates
author: Pong, Lian Yih
date: 2020-05-20
txt: ./txt/cord-306204-rkher4ly.txt
cache: ./cache/cord-306204-rkher4ly.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32467721/
doi: 10.1186/s13020-020-00329-7
summary:
  Vero cells grown in 24-well plates were infected with 30-50 FFU of DENV-2 in the presence or absence of BDTF, PDTF, methanol crude extracts, tannic acids of FT and ST at maximum non-toxic concentration (MNTC) of 100 µg/ mL, 50 µg/mL, 200 µg/mL, 50 µg/mL and 25 µg/mL respectively for 1 h at 4 °C. To study whether tannins in the porcupine dates are bioactive against dengue infection, we have isolated the tannin fractions from MBD and MPD for Besides that, both BDTF and PDTF demonstrated similar and higher virucidal activity against DENV-2 when compared to their methanol crude extracts. " indicates not significant Fig. 9 Effect of pre-treatment with porcupine dates extracts and tannic acids on DENV-2 infection in Vero cells. The antiviral activity ascribed to the interaction between the extracts and host cells was also investigated; pre-treating the cells with BDTF prevented the DENV-2 infection by at least 75% and similar result was observed for FT tannic acid.

abstract:
  BACKGROUND: Dengue fever is currently endemic in tropical and subtropical countries worldwide and effective drug against DENV infection is still unavailable. Porcupine dates, which are traditionally used to treat dengue fever, might contain potential anti-dengue compounds. Two porcupine dates, black date (BD) and powdery date (PD) from Himalayan porcupine (Hystrix brachyura), were investigated for their antiviral activities against DENV-2 in vitro. METHODS: The methanol crude extracts (MBD and MPD) were prepared from the raw material of porcupine dates. The tannin-rich fractions (BDTF and PDTF) were isolated from their methanol crude extracts using column chromatography. The presence of tannins in BDTF and PDTF extracts was determined by fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses. The cytotoxicity and anti-DENV-2 activities including virus yield inhibition, virucidal, virus attachment and pre-treatment assays of the extracts were examined in Vero cells. RESULTS: Our findings revealed that all the extracts of porcupine dates exhibited antiviral activity against DENV-2 in Vero cells. The IC(50) of BDTF and PDTF were 25 µg/mL and 11 µg/mL respectively, while their methanol crude extracts demonstrated lower antiviral efficacy (IC(50) ≈ 101–107 µg/mL). BDTF and PDTF also exerted a similar higher virucidal effect (IC(50) of 11 µg/mL) than methanol crude extracts (IC(50) ≈ 52–66 µg/mL). Furthermore, all the extracts inhibited the attachment of DENV-2 by at least 80%. Pre-treatments of cells with BDTF and PDTF markedly prevented DENV-2 infection when compared to methanol crude extracts. CONCLUSION: This study suggests that porcupine dates possess antiviral properties against DENV-2, which is attributed to its tannin compounds.


id: cord-307219-okvvajms
title: First autochthonous dengue outbreak in Italy, August 2020
author: Lazzarini, Luca
date: 2020-09-10
txt: ./txt/cord-307219-okvvajms.txt
cache: ./cache/cord-307219-okvvajms.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.2807/1560-7917.es.2020.25.36.2001606
doi: 10.2807/1560-7917.es.2020.25.36.2001606
summary:
  In August 2020, during the coronavirus disease (COVID-19) pandemic, five locally acquired cases of dengue virus type 1 were detected in a family cluster in Vicenza Province, North-East Italy where Aedes albopictus mosquitoes are endemic. In August 2020, during the coronavirus disease (COVID-19) pandemic, five locally acquired cases of dengue virus type 1 were detected in a family cluster in Vicenza Province, North-East Italy where Aedes albopictus mosquitoes are endemic. She was investigated for West Nile virus, Usutu virus, dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV) by molecular and serology testing, because she reported that a family member (Case 1) had had similar symptoms after a recent travel in Indonesia. The surveillance, active between June and November, aims to increase the detection rate of DENV and CHIKV (since 2015, also ZIKV) infection in travellers from endemic areas and to promptly identify potential autochthonous cases.

abstract:
  In August 2020, during the coronavirus disease (COVID-19) pandemic, five locally acquired cases of dengue virus type 1 were detected in a family cluster in Vicenza Province, North-East Italy where Aedes albopictus mosquitoes are endemic. The primary case was an importation from West Sumatra, Indonesia. This is the first outbreak of autochthonous dengue reported in Italy. During the COVID-19 pandemic, screening of febrile travelers from endemic countries is crucial in areas where competent vectors are present.


id: cord-317169-qlqavi4t
author: Chiow, K.H.
date: 2015-12-19
txt: ./txt/cord-317169-qlqavi4t.txt
cache: ./cache/cord-317169-qlqavi4t.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26851778/
doi: 10.1016/j.apjtm.2015.12.002
summary:
  (Saururaceae) and three of its constituent flavonoids (quercetin, quercitrin and rutin) against murine coronavirus and dengue virus (DENV). cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2). Certain flavonoids exhibited comparatively weaker antiviral activity, notably quercetin which could inhibit both MHV and DENV-2. This was followed by quercitrin which could inhibit DENV-2 but not MHV, whereas rutin did not exert any inhibitory effect on either virus. cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vivo. cordata exhibited anti-MHV activity at a MIC of 0.98 mg/mL without any apparent cytotoxic effects on CCL9.1 cells. cordata and its flavonoid component, quercetin, could inhibit both MHV and DENV-2 in vitro. Houttuynia cordata extracts and constituents inhibit the infectivity of dengue virus type 2 in vitro

title:
  Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection

abstract:
  OBJECTIVE: To evaluate the in vitro activities of the ethyl acetate (EA) fraction of Houttuynia cordata (H. cordata) Thunb. (Saururaceae) and three of its constituent flavonoids (quercetin, quercitrin and rutin) against murine coronavirus and dengue virus (DENV). METHODS: The antiviral activities of various concentrations of the EA fraction of H. cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2). Cinanserin hydrochloride was also tested against MHV. The EA fraction of H. cordata was tested for acute oral toxicity in C57BL/6 mice. RESULTS: The EA fraction of H. cordata inhibited viral infectivity up to 6 d. Cinanserin hydrochloride was able to inhibit MHV for only 2 d. The 50% inhibitory concentrations (IC(50)) of the EA fraction of H. cordata added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2 with absence of cytotoxicity. The mice fed with the EA fraction up to 2 000 mg/kg did not induce any signs of acute toxicity, with normal histological features of major organs. Certain flavonoids exhibited comparatively weaker antiviral activity, notably quercetin which could inhibit both MHV and DENV-2. This was followed by quercitrin which could inhibit DENV-2 but not MHV, whereas rutin did not exert any inhibitory effect on either virus. When quercetin was combined with quercitrin, enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed. However, the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction. CONCLUSIONS: The compounds in H. cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vivo. H. cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.


id: cord-318120-vfznyyz6
author: Dauner, Allison L.
date: 2015-05-15
txt: ./txt/cord-318120-vfznyyz6.txt
cache: ./cache/cord-318120-vfznyyz6.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0732889315001571
doi: 10.1016/j.diagmicrobio.2015.05.004
summary:
  title: Development of a pan-serotype reverse transcription loop-mediated isothermal amplification assay for the detection of dengue virus To facilitate needed diagnosis, we developed and optimized a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that detects all 4 serotypes of dengue virus (DENV). Development of simple and rapid assay to detect viral RNA of tick-borne encephalitis virus by reverse transcription-loop-mediated isothermal amplification A real-time reverse transcription loop-mediated isothermal amplification assay for the rapid detection of yellow fever virus Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Rapid detection and differentiation of dengue virus serotypes by a real-time reverse transcription-loopmediated isothermal amplification assay Development and evaluation of reverse transcription-loop-mediated isothermal amplification assay for rapid and real-time detection of Japanese encephalitis virus

title:
  Development of a pan-serotype reverse transcription loop-mediated isothermal amplification assay for the detection of dengue virus

abstract:
  During dengue outbreaks, acute diagnosis at the patient's point of need followed by appropriate supportive therapy reduces morbidity and mortality. To facilitate needed diagnosis, we developed and optimized a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that detects all 4 serotypes of dengue virus (DENV). We used a quencher to reduce nonspecific amplification. The assay does not require expensive thermocyclers, utilizing a simple water bath to maintain the reaction at 63 °C. Results can be visualized using UV fluorescence, handheld readers, or lateral flow immunochromatographic tests. We report a sensitivity of 86.3% (95% confidence interval [CI], 72.7–94.8%) and specificity of 93.0% (95% CI, 83.0–98.1%) using a panel of clinical specimens characterized by DENV quantitative reverse transcription–polymerase chain reaction. This pan-serotype DENV RT-LAMP can be adapted to field-expedient formats where it can provide actionable diagnosis near the patient's point of need.


id: cord-318614-518giv0m
author: Tsai, Jih-Jin
date: 2019-07-10
txt: ./txt/cord-318614-518giv0m.txt
cache: ./cache/cord-318614-518giv0m.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pone.0218139
doi: 10.1371/journal.pone.0218139
summary:
  A pan-dengue virus (DENV) RT-iiPCR, targeting the 5'' untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease. Testing with the pan-DENV RT-iiPCR, the analytical and clinical performance of the fully automatic POCKIT Central system was comparable to those of the semi-automatic POCKI combo system, which was validated previously to offer performances equivalent to the CDC DENV1-4 real-time RT-PCR for the detection of DENV in human serum [7, 24, 26] .

title:
  A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos

abstract:
  BACKGROUND: The insulated isothermal PCR (iiPCR) technology enables consistent PCR amplification and detection in a simple heating device. A pan-dengue virus (DENV) RT-iiPCR, targeting the 5’ untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. Working on the same technologies, a compact automated sample-in-answer-out system (POCKIT Central Nucleic Acid Analyser) has been available commercially for iiPCR, minimizing human error risks and allowing easy molecular bio-detection near points of need. Here, we evaluated the analytical and clinical performance of the pan-DENV RT-iiPCR on the fully automated system by comparison to those on the semi-automated system. METHODOLOGY/PRINCIPAL FINDINGS: Testing sera containing serial diluted DENV-1, -2, -3, or -4 cell culture stock, the pan-DENV RT-iiPCR system had similar 100% detection endpoints on the two systems; i.e. at 1, 10, 1 and 10 PFU/ml, respectively, on the fully automated system, and at 10, 1, 10 and 10 PFU/ml, respectively, on the semi-automated system. Furthermore, both fully automated and semi-automated PCR system can detect all four DENV serotypes in mosquitos. Clinical performance of the reagent on the two systems was evaluated by testing 60 human serum samples. Both systems detected the same 40 samples (ten DENV-1, -2, -3, and -4 positive each) and did not detect the other 20; 100% agreement (κ = 1) was found between the two systems. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease.


id: cord-319174-pbqjg7hf
title: A novel reporter system for neutralizing and enhancing antibody assay against dengue virus
author: Song, Ke-Yu
date: 2014-02-18
url: https://doi.org/10.1186/1471-2180-14-44
doi: 10.1186/1471-2180-14-44
abstract:
  BACKGROUND: Dengue virus (DENV) still poses a global public health threat, and no vaccine or antiviral therapy is currently available. Antibody plays distinct roles in controlling DENV infections. Neutralizing antibody is protective against DENV infection, whereas sub-neutralizing concentration of antibody can increase DENV infection, termed antibody-dependent enhancement (ADE). Plaque-based assay represents the most widely accepted method measuring neutralizing or enhancing antibodies. RESULTS: In this study, a novel reporter virus-based system was developed for measuring neutralization and ADE activity. A stable Renilla luciferase reporter DENV (Luc-DENV) that can produce robust luciferase signals in BHK-21 and K562 cells were used to establish the assay and validated against traditional plaque-based assay. Luciferase value analysis using various known DENV-specific monoclonal antibodies showed good repeatability and a well linear correlation with conventional plaque-based assays. The newly developed assay was finally validated with clinical samples from infected animals and individuals. CONCLUSIONS: This reporter virus-based assay for neutralizing and enhancing antibody evaluation is rapid, lower cost, and high throughput, and will be helpful for laboratory detection and epidemiological investigation for DENV antibodies.


id: cord-320091-2lrqubdl
author: Badawi, Alaa
date: 2018-07-10
url: https://doi.org/10.1371/journal.pone.0200200
doi: 10.1371/journal.pone.0200200
title:
  Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis

abstract:
  BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m(2), prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.


id: cord-326840-piv6h7oq
author: Paemanee, Atchara
date: 2018-05-16
url: https://www.ncbi.nlm.nih.gov/pubmed/29769094/
doi: 10.1186/s13104-018-3417-3
title:
  Screening of melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity

abstract:
  OBJECTIVE: Infections with the mosquito transmitted dengue virus (DENV) are a significant public health burden in many parts of the world. Despite the introduction of a commercial vaccine in some parts of the world, the majority of the populations at risk of infection remain unprotected against this disease, and there is currently no treatment for DENV infection. Natural compounds offer the prospect of cheap and sustainable therapeutics to reduce the disease burden during infection, and thus potentially alleviate the risk of more severe disease. This study evaluated the potential anti-DENV 2 activity of five natural compounds namely melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol in two different cell lines. RESULTS: Screening of the compounds showed that one compound (acetyl-l-carnitine) showed no effect on DENV infection, three compounds (melatonin, α-tocopherol and folic acid) slightly increased levels of infection, while the 5th compound, resveratrol, showed some limited anti-DENV activity, with resveratrol reducing virus output with an EC(50) of less than 25 μM. These results suggest that some commonly taken natural compounds may have beneficial effects on DENV infection, but that others may potentially add to the disease burden. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3417-3) contains supplementary material, which is available to authorized users.


id: cord-328661-spxgox52
author: Yu, Jianhai
date: 2019-08-05
txt: ./txt/cord-328661-spxgox52.txt
cache: ./cache/cord-328661-spxgox52.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31392945/
doi: 10.4269/ajtmh.18-0951
summary:
  The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong. Since 1990, however, DENV1 has been mainly isolated from the infected cases, and its continued existence in Guangdong Province indicated that endemic infectious agents of dengue may be circulating locally. With the epidemiological data since 2005 supplied by the Guangdong Provincial CDC, we studied phylogenetics, molecular characteristics, and epidemiology to strengthen the foundational research of DENV1 for the prevention of large-scale dengue epidemics, providing preventive and control measures of DF with important evidence. Based on representative strains of the E gene in lineages of the 2014 outbreak, as well as the molecular evolution database, we analyzed molecular characterization and possibility of local circulation for DENV1 since 2005 in Guangdong.

title:
  Epidemiological and Evolutionary Analysis of Dengue-1 Virus Detected in Guangdong during 2014: Recycling of Old and Formation of New Lineages

abstract:
  The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.


id: cord-330743-o11d0aa1
author: Yu, Xi
date: 2020-05-25
txt: ./txt/cord-330743-o11d0aa1.txt
cache: ./cache/cord-330743-o11d0aa1.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.22.109900
doi: 10.1101/2020.05.22.109900
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.

title:
  Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

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.


id: cord-342157-qjyooq68
title: Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3
author: King, Chwan-Chuen
date: 2008-05-21
txt: ./txt/cord-342157-qjyooq68.txt
cache: ./cache/cord-342157-qjyooq68.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/18495043/
doi: 10.1186/1743-422x-5-63
summary:
  In our study, complete genomic sequencing of DENV-3 strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the DENV genome other than within the E gene were also analyzed. RESULTS: Using maximum likelihood and Bayesian approaches, our phylogenetic analysis revealed that the Taiwan''s indigenous DENV-3 isolated from 1994 and 1998 dengue/DHF epidemics and one 1999 sporadic case were of the three different genotypes – I, II, and III, each associated with DENV-3 circulating in Indonesia, Thailand and Sri Lanka, respectively. Compared to the prototype strain H87, several unique amino acid substitutions that serve as unique signature sites for each genotype were found within the full genomic sequences of the selected DENV-3 isolates from Taiwan or other countries and are listed by the order of the gene in Table 3 .

abstract:
  BACKGROUND: Although the previous study demonstrated the envelope protein of dengue viruses is under purifying selection pressure, little is known about the genetic differences of full-length viral genomes of DENV-3. In our study, complete genomic sequencing of DENV-3 strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the DENV genome other than within the E gene were also analyzed. RESULTS: Using maximum likelihood and Bayesian approaches, our phylogenetic analysis revealed that the Taiwan's indigenous DENV-3 isolated from 1994 and 1998 dengue/DHF epidemics and one 1999 sporadic case were of the three different genotypes – I, II, and III, each associated with DENV-3 circulating in Indonesia, Thailand and Sri Lanka, respectively. Sequence diversity and selection pressure of different genomic regions among DENV-3 different genotypes was further examined to understand the global DENV-3 evolution. The highest nucleotide sequence diversity among the fully sequenced DENV-3 strains was found in the nonstructural protein 2A (mean ± SD: 5.84 ± 0.54) and envelope protein gene regions (mean ± SD: 5.04 ± 0.32). Further analysis found that positive selection pressure of DENV-3 may occur in the non-structural protein 1 gene region and the positive selection site was detected at position 178 of the NS1 gene. CONCLUSION: Our study confirmed that the envelope protein is under purifying selection pressure although it presented higher sequence diversity. The detection of positive selection pressure in the non-structural protein along genotype II indicated that DENV-3 originated from Southeast Asia needs to monitor the emergence of DENV strains with epidemic potential for better epidemic prevention and vaccine development.


id: cord-344020-8poerd09
title: Autochthonous dengue in two Dutch tourists visiting Département Var, southern France, July 2020
author: Vermeulen, Tom D
date: 2020-10-01
txt: ./txt/cord-344020-8poerd09.txt
cache: ./cache/cord-344020-8poerd09.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33006305/
doi: 10.2807/1560-7917.es.2020.25.39.2001670
summary:
  We report dengue virus (DENV) infection in two Dutch tourists who visited Département Var, southern France, in July and August 2020. We report dengue virus (DENV) infection in two Dutch tourists who visited Département Var, southern France, in July and August 2020. As some autochthonous dengue cases have occurred in Europe in recent years, awareness among physicians and public health experts about possible intermittent presence of DENV in southern Europe is important to minimise delay in diagnosis and treatment. As some autochthonous dengue cases have occurred in Europe in recent years, awareness among physicians and public health experts about possible intermittent presence of DENV in southern Europe is important to minimise delay in diagnosis and treatment. On August 27, upon confirmation of the serological results, Patient 1 was reported by the RIVM to the French authorities through the Early Warning and Response System of the European Union as an autochthonous DENV infection probably acquired in France with cross-border implication.

abstract:
  We report dengue virus (DENV) infection in two Dutch tourists who visited Département Var, southern France, in July and August 2020. As some autochthonous dengue cases have occurred in Europe in recent years, awareness among physicians and public health experts about possible intermittent presence of DENV in southern Europe is important to minimise delay in diagnosis and treatment. Quick diagnosis can lead to timely action to contain the spread of vector-borne diseases and minimise transmission.


id: cord-345898-a6vt8kso
title: Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses
author: Ren, Linzhu
date: 2016-01-04
txt: ./txt/cord-345898-a6vt8kso.txt
cache: ./cache/cord-345898-a6vt8kso.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12010-015-1968-5
doi: 10.1007/s12010-015-1968-5
summary:
  There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. An RVP is a type of virus-like particle (VLP) composed of viral structural proteins and a self-replicating replicon RNA containing a reporter gene [17, 63] . However, when the cells were infected with the specific virus, the viral RdRp was provided by the virus and the defective replicon was activated, resulting in high-level expression of the reporter gene, which could be easily examined [44] . However, when the cells were infected with the specific virus, the viral RdRp was provided by the virus and the defective replicon was activated, resulting in high-level expression of the reporter gene, which could be easily examined [44] . Development of Dengue type-2 virus replicons expressing GFP reporter gene in study of viral RNA replication

abstract:
  Cell-based reporter systems have facilitated studies of viral replication and pathogenesis, virus detection, and drug susceptibility testing. There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. The first type is classical reporter system, which relies on recombinant virus, reporter virus particle, or subgenomic replicon. During infection with the recombinant virus or reporter virus particle, the reporter protein is expressed and can be detected in real time in a dose-dependent manner. Using subgenomic replicon, which are genetically engineered viral RNA molecules that are capable of replication but incapable of producing virions, the translation and replication of the replicon could be tracked by the accumulation of reporter protein. The second type of reporter system involves genetically engineered cells bearing virus-specific protease cleavage sequences, which can sense the incoming viral protease. The third type is based on viral replicase, which can report the specific virus infection via detection of the incoming viral replicase. This review specifically focuses on the major technical breakthroughs in the design of cell-based reporter systems and the application of these systems to the further understanding and control of viruses over the past few decades.


id: cord-353241-ityhcak7
title: IoT PCR for pandemic disease detection and its spread monitoring
author: Zhu, Hanliang
date: 2020-01-15
txt: ./txt/cord-353241-ityhcak7.txt
cache: ./cache/cord-353241-ityhcak7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0925400519312973
doi: 10.1016/j.snb.2019.127098
summary:
  Considerable effort has been invested in the development of portable, user-friendly, and cost-effective systems for point-of-care (POC) diagnostics, which could also create an Internet of Things (IoT) for healthcare via a global network. Connecting the easy to use and cost-effective POC devices providing the DENV diagnoses via a mobile network would create an Internet of Things (IoT) [15] for healthcare [16, 17] , an essential tool to tackle any infectious disease outbreak. Prior to testing on an IoT PCR device, we verified the master mix performance and its values of critical threshold (C T ) and the melting temperature (T M ) using a commercial real-time PCR system (Supplementary Section A) beginning with a hot start at 95°C for 30 s followed by 40 cycles of PCR amplification consisting of DNA denaturation at 95°C for 8 s, primer annealing at 60°C for 30 s, and DNA sequence elongation at 72°C for 10 s, then followed by melting curve analysis (MCA) from 72°C to 95°C.

abstract:
  During infectious disease outbreaks, the centers for disease control need to monitor particular areas. Considerable effort has been invested in the development of portable, user-friendly, and cost-effective systems for point-of-care (POC) diagnostics, which could also create an Internet of Things (IoT) for healthcare via a global network. However, at present IoT based on a functional POC instrument is not available. Here we show a fast, user-friendly, and affordable IoT system based on a miniaturized polymerase chain reaction device. We demonstrated the system’s capability by amplification of complementary deoxyribonucleic acid (cDNA) of the dengue fever virus. The resulting data were then automatically uploaded via a Bluetooth interface to an Android-based smartphone and then wirelessly sent to a global network, instantly making the test results available anywhere in the world. The IoT system presented here could become an essential tool for healthcare centers to tackle infectious disease outbreaks identified either by DNA or ribonucleic acid.


id: cord-355179-wmfwl2bh
author: Jung, Eunhye
date: 2019-06-18
txt: ./txt/cord-355179-wmfwl2bh.txt
cache: ./cache/cord-355179-wmfwl2bh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31213630/
doi: 10.1038/s41598-019-45095-1
summary:
  Overall, the data indicate that the antiviral activity of niclosamide during the early stage of the DENV life cycle correlates with the neutralization profile of the low-pH compartments, suggesting that blocking endosomal acidification results in the inhibition of viral genome replication and polyprotein processing, which further impedes viral protein expression and virus production. In this study, we found that neutralization of low-pH intracellular compartments by niclosamide not only inhibited the early stage of the DENV viral life cycle, such as viral RNA replication, independent of the entry step but also the late stage, specifically, the maturation of virus particles into infectious virions. Indeed, niclosamide treatment www.nature.com/scientificreports www.nature.com/scientificreports/ during the first 6 h of infection reduced DENV replication in BHK-21 cells harbouring dengue replicons to a level comparable to that of ribavirin, suggesting that the drug affects viral RNA replication and/or translation independent of its effect on entry, membrane fusion and genome release.

title:
  Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro

abstract:
  Dengue fever is one of the most important mosquito-borne viral infections in large parts of tropical and subtropical countries and is a significant public health concern and socioeconomic burden. There is an urgent need to develop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load. Niclosamide, an antiparasitic drug approved for human use, has been recently identified as an effective antiviral agent against a number of pH-dependent viruses, including flaviviruses. Here, we reveal that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Specifically, niclosamide-induced endosomal neutralization not only prevents viral RNA replication but also affects the maturation of DENV particles, rendering them non-infectious. We found that niclosamide-induced endosomal neutralization prevented E glycoprotein conformational changes on the virion surface of flaviviruses, resulting in the release of non-infectious immature virus particles with uncleaved pr peptide from host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug.


id: cord-355489-tkvfneje
title: Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia
author: Mendez, Jairo A
date: 2010-09-14
txt: ./txt/cord-355489-tkvfneje.txt
cache: ./cache/cord-355489-tkvfneje.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1743-422x-7-226
doi: 10.1186/1743-422x-7-226
summary:
  Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Due to the importance of DENV in public health, the particular goals of this research were to reconstruct the phylogenetic history of DENV-1 and to date the phylogenetic tree using isolation time as calibration points to establish date of introduction of virus and rate evolution patterns of virus in Colombia. Previously reported genotypes were represented in the tree and placed most of the Colombian isolates nesting in the genotype V clade (America, Africa) and were closely related to Argentina, Brazil and Paraguay virus strains.

abstract:
  BACKGROUND: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70's when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. RESULTS: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major aminoacid changes in the analyzed region were found. CONCLUSION: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages.


id: cord-355610-7xy4s483
author: Hu, Dan
date: 2019-06-26
url: https://www.ncbi.nlm.nih.gov/pubmed/31242272/
doi: 10.1371/journal.ppat.1007836
title:
  A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III

abstract:
  Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.


id: cord-355906-yeaw9nr8
title: Tackling dengue fever: Current status and challenges
author: Nedjadi, Taoufik
date: 2015-12-09
url: https://www.ncbi.nlm.nih.gov/pubmed/26645066/
doi: 10.1186/s12985-015-0444-8
abstract:
  According to recent statistics, 96 million apparent dengue infections were estimated worldwide in 2010. This figure is by far greater than the WHO prediction which indicates the rapid spread of this disease posing a growing threat to the economy and a major challenge to clinicians and health care services across the globe particularly in the affected areas. This article aims at bringing to light the current epidemiological and clinical status of the dengue fever. The relationship between genetic mutations, single nucleotide polymorphism (SNP) and the pathophysiology of disease progression will be put into perspective. It will also highlight the recent advances in dengue vaccine development. Thus far, a significant progress has been made in unraveling the risk factors and understanding the molecular pathogenesis associated with the disease. However, further insights in molecular features of the disease and the development of animal models will enormously help improving the therapeutic interventions and potentially contribute to finding new preventive measures for population at risk.


