Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 58 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 8336 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 46 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 58 IAV 16 virus 10 Fig 7 infection 7 cell 6 influenza 6 IFN 5 figure 5 IFITM3 4 SARS 4 PR8 4 MERS 4 H1N1 3 a549 3 RSV 2 RNA 2 MDCK 2 Influenza 2 HIV-1 2 H5N1 1 week 1 viral 1 type 1 swine 1 sars2 1 sample 1 rig 1 response 1 pregnant 1 pig 1 peptide 1 olaparib 1 model 1 mannose 1 lung 1 lectin 1 inflammasome 1 increase 1 hct 1 exhibition 1 entry 1 curcumin 1 com 1 bind 1 bal 1 ZIKV 1 Wnt 1 WSN 1 WIV 1 USA Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 6302 virus 4677 cell 3334 influenza 3305 infection 2090 protein 1149 response 1136 swine 1109 mouse 1028 study 997 receptor 941 lung 930 host 887 expression 880 gene 785 activity 775 type 763 % 751 level 687 effect 630 activation 624 pathway 618 role 613 replication 591 pig 572 disease 570 factor 531 acid 521 model 514 membrane 504 strain 482 treatment 478 production 469 pandemic 466 antibody 464 vaccine 462 entry 454 apoptosis 450 iav 440 macrophage 435 analysis 432 figure 421 sample 420 lectin 417 interaction 417 cytokine 415 group 413 inhibition 411 function 410 inhibitor 396 result Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 3192 IAV 1381 al 1093 et 1015 . 727 H1N1 711 Fig 678 HA 594 IFN 566 NA 559 A 542 Influenza 534 T 476 RNA 432 SP 392 IFITM3 379 NP 361 CD8 329 H3N2 295 H5N1 288 D 275 PR8 275 C 273 SARS 236 CoV 233 HIV-1 228 RSV 217 MBL 214 MERS 209 PA 198 A(H1N1)pdm09 190 MDCK 186 TNF 181 TRAIL 178 DC 162 H1N2 153 GM 147 PCR 144 B 134 M2 134 II 131 USA 130 China 128 SA 127 CoV-2 124 H7N9 122 CSF 121 PB2 121 ACA 120 Nrf2 118 PKR Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 985 we 578 it 408 i 187 they 45 them 27 ifitm3 24 us 23 itself 8 you 6 one 5 themselves 4 he 3 hifnα 1 ≤4 1 ybbr 1 t2aecs 1 she 1 s 1 mrnas 1 mir410 1 imagej 1 ilc1s 1 ifitms 1 iavpp 1 https://doi.org/10.1371/journal.pone.0212757.g004 1 esat6 1 cdc42 1 bay117082 1 a1-antitrypsin Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 12096 be 2095 have 1202 use 1009 induce 955 show 954 bind 722 increase 721 infect 600 inhibit 557 mediate 525 associate 498 include 481 signal 470 follow 442 suggest 426 identify 420 report 413 find 382 lead 374 reduce 372 do 364 detect 356 observe 347 activate 331 result 331 determine 324 contain 316 indicate 308 compare 298 cause 283 express 279 require 275 regulate 273 decrease 271 demonstrate 267 provide 266 describe 262 enhance 259 base 240 promote 237 target 236 perform 227 involve 224 affect 217 contribute 216 treat 204 link 204 block 197 obtain 197 know Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 1920 viral 1191 human 1070 - 1037 not 1015 also 926 respiratory 646 immune 620 antiviral 616 high 603 specific 539 other 503 however 484 avian 482 different 455 more 452 well 425 low 409 severe 404 anti 392 inflammatory 391 epithelial 374 such 357 only 348 like 342 cellular 320 most 315 dependent 295 further 294 first 286 innate 283 acute 273 positive 267 as 260 thus 254 similar 253 non 252 infected 250 important 248 significantly 248 highly 247 novel 245 multiple 245 clinical 239 early 238 several 221 then 218 single 214 significant 214 pulmonary 213 a549 Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 93 most 50 high 37 least 22 Most 21 good 7 low 7 large 5 miR-193b 5 late 4 strong 3 vRNA 3 great 3 close 1 M 1 Ø299A 1 weak 1 vRNPs 1 small 1 short 1 new 1 full 1 few 1 factorsb 1 early 1 deadly 1 cold 1 clear 1 cheap 1 broad 1 bad 1 Y296A 1 Rab7-positive 1 -A2 Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 227 most 47 least 4 well 4 mir-193b 2 α2-ar 2 vrna 1 youngest 1 shortest 1 highest 1 fast Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 26 doi.org 3 www.mdpi.com 3 www.fludb.org 3 creativecommons.org 2 www.signalingpathways.org 1 www.who.int 1 www.targetscan.org 1 www.functionalglycomics.org 1 www.fao.org 1 www.ebi.ac.uk 1 www.cbs.dtu.dk 1 ww.signalingpathways.org 1 tiny.cc 1 tiny 1 pictar.mdc-berlin 1 pathospot.org 1 orcid.org 1 ndexbio.org 1 itve.dk 1 hannonlab.cshl.edu 1 fiji.sc 1 dx 1 diana.imis.athena-innovation.gr 1 covid19.who.int 1 chopchop.cbu.uib.no 1 bit.ly 1 advances.sciencemag.org Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 6 http://doi.org/10.1101/2020.04 6 http://doi.org/10.1101 3 http://www.fludb.org 3 http://doi.org/10.1101/2020.04.21.20073072 3 http://creativecommons.org/licenses/by/4.0/ 2 http://doi.org/10.1038/s41598-020-58588-1 1 http://www.who.int/csr/disease/ 1 http://www.targetscan.org/ 1 http://www.signalingpathways.org/index.jsf 1 http://www.signalingpathways.org/docs/ 1 http://www.mdpi.com/1999-4915/12/9/1013/s1 1 http://www.mdpi.com/1999-4915/12/6/679/s1 1 http://www.mdpi.com/1999-4915/11/6/548/s1 1 http://www.functionalglycomics.org 1 http://www.fao.org/ag/againfo/programmes/en/empres/h7n9/ 1 http://www.ebi.ac.uk/ 1 http://www.cbs.dtu.dk/services/NetNGlyc/ 1 http://ww.signalingpathways.org 1 http://tiny.cc/2i56rz 1 http://tiny 1 http://pictar.mdc-berlin 1 http://pathospot.org 1 http://orcid.org/0000-0002-4811-4897 1 http://ndexbio.org 1 http://itve.dk/ 1 http://hannonlab.cshl.edu/fastx_toolkit 1 http://fiji.sc/ 1 http://dx 1 http://doi.org/10.1371/journal.pone.0212757.g006 1 http://doi.org/10.1371/journal.pone.0212757.g004 1 http://doi.org/10.1371/journal.pone.0212757.g003 1 http://doi.org/10.1371/journal.pone.0212757.g002 1 http://doi.org/10.1371/journal.pone.0212757.g001 1 http://doi.org/10.1371/journal.pone.0188251.g010 1 http://doi.org/10.1038/s41597-020-00628-6 1 http://doi.org/10.1038/s41401-020-0403-9 1 http://doi.org/10 1 http://diana.imis.athena-innovation.gr/ 1 http://covid19.who.int/ 1 http://chopchop.cbu.uib.no/ 1 http://bit.ly/30nN129 1 http://advances.sciencemag.org/cgi/ Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 1 torr0033@umn.edu Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 12 virus infected cells 9 cells were then 8 receptor binding specificity 7 cells are critical 6 proteins mediate cellular 5 cells was also 5 iav infected a549 5 protein induces apoptosis 5 studies have also 5 virus activates inflammasomes 5 virus binding rate 5 viruses using reverse 4 cells did not 4 cells were further 4 infection has also 4 mice were randomly 4 proteins were significantly 4 study did not 4 virus did not 4 virus does not 4 virus was also 4 viruses do not 3 activation is essential 3 cell signaling pathways 3 cells are more 3 cells were more 3 effect was not 3 expression was also 3 iav did not 3 iav infected swine 3 iav was first 3 infection is not 3 mice are more 3 mice were intranasally 3 protein inhibits early 3 proteins were similarly 3 receptors were predominant 3 responses cause lethal 3 study are available 3 virus binding assays 3 virus infected mice 3 virus inhibits type 3 virus was first 3 viruses is not 3 viruses reported earlier 3 viruses were also 2 cells are also 2 cells are capable 2 cells are large 2 cells following iav Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 2 iav had no effect 2 infection is not well 2 response has not only 1 cells are not primary 1 cells did not significantly 1 cells showed no significant 1 cells were not feasible 1 effect has not only 1 effect was not absolute 1 gene is not essential 1 gene is not specific 1 ha is not frequently 1 iav are not fully 1 iav had no impacts 1 iav is not fully 1 infection had no effect 1 infection is not fully 1 mice are not capable 1 mice are not susceptible 1 mice do not accurately 1 mice had no effect 1 protein showed no weight 1 studies is not clear 1 study found no link 1 study reported no effect 1 study showing no effect 1 virus had not yet 1 virus is not fully 1 viruses do not only 1 viruses do not usually 1 viruses is not fully 1 viruses is not long A rudimentary bibliography -------------------------- id = cord-300423-q2i328sz author = Bai, Lei title = Co-infection of influenza A virus enhances SARS-CoV-2 infectivity date = 2020-10-14 keywords = IAV; SARS summary = Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. The results demonstrate that the pre-infection of 57 IAV strongly enhances the infectivity of SARS-CoV-2 by boosting viral entry in the cells 58 and by elevating viral load plus more severe lung damage in infected mice. We 75 further tested more cell lines to show that the enhancement of the pSARS-CoV-2 infectivity 76 by IAV was a general effect although the increased folds were different (lower basal level 77 of infectivity, higher enhancement fold) (Fig.1D ). We found that the pre-infection of IAV 80 strongly increased the copy numbers of the SARS-CoV-2 genome (E and N genes) in both 81 cell lysates and supernatants of A549 (~15 folds) (Fig.1F) . The histological data in Fig. 2D further illustrated that IAV and 98 SARS-CoV-2 co-infection induced more severe lung pathologic changes with massive 99 infiltrating cells and obvious alveolar necrosis as compared to SARS-CoV-2 single 100 infection or mock infection. doi = 10.1101/2020.10.14.335893 id = cord-003498-4ct0ywnw author = Bdeir, Najat title = A system for production of defective interfering particles in the absence of infectious influenza A virus date = 2019-03-01 keywords = DI-244; IAV; MDCK; PB2 summary = Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. Here, we investigated whether coexpression of wt segments 2-8, PB2 protein and DI-244 RNA allows for production of DIPs. Employing a novel DI-244 variant encoding mScarlet-i, we show that DI-244-based DIPs are efficiently produced in cells expressing a codon optimized version of PB2 and that these DIPs exert potent antiviral activity. Influenza A viruses A/Panama/2007/99 (H3N2) [24] and A/PR/8/34 (H1N1) produced in embryonated chicken eggs were used to assess the antiviral activity of DIPs. We further employed a recombinant vesicular stomatitis virus (VSV) that expresses a dual reporter consisting of eGFP and firefly luciferase from an additional transcription unit located between the open reading frames for the viral glycoprotein and polymerase [27] . doi = 10.1371/journal.pone.0212757 id = cord-013174-whg64w0w author = Bhatta, Tarka Raj title = Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype date = 2020-09-10 keywords = IAV; pig; week summary = doi = 10.3390/v12091013 id = cord-307148-k1uo3fxm author = Bradshaw, Patrick C. title = COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm date = 2020-09-09 keywords = BHB; COVID-19; IAV; NADPH; ROS; SARS; cell; increase summary = R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. Others have also suggested that increasing systemic ketone levels may aid host defenses against respiratory viral infection, in part, by decreasing inflammation [1, 2] , including a recent comprehensive review [3] , while a clinical trial of the effects of a ketogenic diet on intubated SARS-CoV-2 patients has recently been registered (NCT04358835). Coronaviruses have been shown to increase the oxidation of phospholipids, which stimulate toll-like receptor 4 (TLR4) signaling on macrophages, leading to cytokine production and acute lung injury [163] , so HDAC inhibition with R-BHB appears to be a viable treatment to decrease cytokine levels and inflammation. doi = 10.1155/2020/6401341 id = cord-335871-zieuc7vk author = Brazee, Patricia L. title = Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury date = 2020-05-13 keywords = IAV; LUBAC; infection; response summary = doi = 10.1016/j.arbres.2020.04.019 id = cord-314825-fzba05wn author = Chauhan, Ravendra P. title = A Systematic Review Analyzing the Prevalence and Circulation of Influenza Viruses in Swine Population Worldwide date = 2020-05-08 keywords = H1N1; H1N2; H3N2; IAV; IDV; swine; virus summary = doi = 10.3390/pathogens9050355 id = cord-324696-htx0ul4o author = Chothe, Shubhada K. title = Avian and human influenza virus compatible sialic acid receptors in little brown bats date = 2017-04-06 keywords = IAV; virus summary = doi = 10.1038/s41598-017-00793-6 id = cord-275821-yu39aw54 author = Ciminski, Kevin title = Novel insights into bat influenza A viruses date = 2017-09-14 keywords = IAV; virus summary = doi = 10.1099/jgv.0.000927 id = cord-003870-hr99dwi7 author = Clohisey, Sara title = Host susceptibility to severe influenza A virus infection date = 2019-09-05 keywords = H1N1; IAV; IFITM3; influenza summary = Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. Factors predicted to confer more specific susceptibility to influenza are placed higher in the diagram independently associated with severe disease from either seasonal or pandemic IAV [24] . Susceptibility to severe H1N1 infection was analysed in a recent genome-wide study (integrated with data on genetic variants associated with altered gene expression) which implicated an intronic SNP of GLDC, rs1755609-G [80] . Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). doi = 10.1186/s13054-019-2566-7 id = cord-004280-c470nlie author = Coleman, Kristen K. title = Airborne Influenza A Virus Exposure in an Elementary School date = 2020-02-05 keywords = IAV; RNA; influenza; virus summary = In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school. Significantly different (p = 0.049) airborne IAV densities were detected between all three indoor locations (i.e., gymnasium, classroom, and corridor) and all positive samples were collected during the last two weeks of 66 , and a 20-30% relative humidity level; Descriptive of an average elementary school student in the USA weighing ~23-32 kg with an assumed tidal volume (V T ) of 7 mL per kg of body mass. Given the high airborne IAV densities detected in the school corridor, along with elevated student contact rates, it is plausible to conclude that the school corridor is a "hotspot" for influenza virus transmission. doi = 10.1038/s41598-020-58588-1 id = cord-004018-33zi29bg author = Coombs, Kevin M. title = Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses date = 2019-11-05 keywords = H5N1; H7N9; IAV; PR8 summary = doi = 10.3390/v11111028 id = cord-325192-italbsed author = Desai, Tanay M. title = IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion date = 2014-04-03 keywords = Fig; IAV; IFITM3; MDCK; a549; cell summary = doi = 10.1371/journal.ppat.1004048 id = cord-309010-tmfm5u5h author = Dietert, Kristina title = Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia date = 2017-11-20 keywords = Fig; IAV; MERS; model summary = doi = 10.1371/journal.pone.0188251 id = cord-272117-erzpz3c0 author = Downey, Jeffrey title = Dissecting host cell death programs in the pathogenesis of influenza date = 2018-04-18 keywords = IAV; IFN; cell; infection summary = doi = 10.1016/j.micinf.2018.03.005 id = cord-255980-u0c6pg8n author = Du, Lanying title = Development of a safe and convenient neutralization assay for rapid screening of influenza HA-specific neutralizing monoclonal antibodies date = 2010-07-02 keywords = H5N1; IAV summary = Abstract The worldwide outbreak of the swine-origin 2009 H1N1 influenza A virus (IAV) and an increasing number of influenza cases caused by a highly pathogenic avian influenza (HPAI) H5N1 have accelerated the need to develop vaccines and antiviral agents against IAVs. Among various antivirals, neutralizing monoclonal antibodies (mAbs) are considered important passive therapeutics having an immediate effect against viral pathogens. As shown in Fig. 3A , 20 mAbs were initially screened for HA-specific antibody responses, 10 of which with the highest antibody titer were selected to detect neutralizing activity against five pseudoviruses expressing HA of H5N1 IAVs (QH-HA, XJ-HA, AH-HA, HK-HA, 1194-HA), one pseudovirus bearing HA of 2009 epidemic H1N1 IAV (H1N1-HA) ( Table 1) , and the VSV-G pseudovirus in 293T cells since this cell line demonstrated the highest ability to support virus infection. doi = 10.1016/j.bbrc.2010.05.161 id = cord-003598-m2fsrwvw author = Elbahesh, Husni title = Response Modifiers: Tweaking the Immune Response Against Influenza A Virus date = 2019-04-12 keywords = IAV; infection; influenza; virus summary = Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections. Clinical treatment options for severe influenza virus infections remain limited and relying heavily on the administration of antiviral neuraminidase inhibitors (NAIs) and supportive critical care (9). While virus-targeted therapies remain the standard approach, IV''s mutability and adaptation to current antivirals has highlighted the need for new therapeutic options that target host factors that regulate IV infections and resulting immune responses. Host kinases regulate not only IAV entry and replication but also initiate antiviral signaling cascades that regulate expression of pro-inflammatory chemokines and cytokines during infections and present viable targets for intervention (24, (49) (50) (51) (52) (53) (54) (55) (56) (57) (58) . Inhibition of p38 mitogen-activated protein kinase impairs influenza virus-induced primary and secondary host gene responses and protects mice from lethal H5N1 infection doi = 10.3389/fimmu.2019.00809 id = cord-003169-bdw5ke4i author = Guo, Hongbo title = Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces date = 2018-08-13 keywords = Fig; IAV; PR8; WSN summary = doi = 10.1371/journal.ppat.1007233 id = cord-291534-c6cjxq07 author = Gwyer Findlay, Emily title = Cationic Host Defence Peptides: Potential as Antiviral Therapeutics date = 2013-05-07 keywords = HIV-1; HNP1; IAV; LL-37; peptide; virus summary = doi = 10.1007/s40259-013-0039-0 id = cord-002823-n55xvwkf author = Halstead, E. Scott title = GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization date = 2018-01-05 keywords = CSF; DTGM; Fig; IAV; bal summary = The effect of local elevation of GM-CSF on IAV infection in the lung has been investigated in transgenic models with expression of GM-CSF under the control of constitutive or doxycycline-inducible promoters in lungs of alveolar or small airway epithelial cells of GM-CSF knockout (csf2 −/− ) mice [3, 4] . To examine the mechanism of protection conferred by therapeutic GM-CSF levels, we measured respiratory and biochemical parameters of lower airway disease, and analyzed the transcriptome of FACS-sorted AMs and exudative macrophages (EM) from IAV-infected mice. IPA also predicted the activation of the IL-10 receptor alpha-chain in both AMs and EMs. Given that IL-10 levels in BAL fluid were not elevated in DTGM as compared WT mice (Additional file 6: Figure S4D ), it is possible that GM-CSF overexpressing during IAV somehow potentiates IL-10 signaling in the lung microenvironment. doi = 10.1186/s12931-017-0708-5 id = cord-267531-tqqj4cy0 author = He, Ying title = A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China date = 2014-05-14 keywords = IAV; RSV; infection summary = doi = 10.1111/irv.12257 id = cord-310780-0k8owwf8 author = Iwai, Atsushi title = Relevance of signaling molecules for apoptosis induction on influenza A virus replication date = 2013-11-22 keywords = IAV; JNK summary = doi = 10.1016/j.bbrc.2013.10.100 id = cord-102586-mx534xbx author = Javaid, W. title = Real Time Investigation of a large Nosocomial Influenza A Outbreak Informed by Genomic Epidemiology date = 2020-05-15 keywords = IAV summary = doi = 10.1101/2020.05.10.20096693 id = cord-332725-2oc1yrzx author = Kosmider, Beata title = Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus date = 2012-06-06 keywords = ATI; ATII; IAV; Nrf2; PR8 summary = doi = 10.1186/1465-9921-13-43 id = cord-003772-1345qct4 author = Kummer, Susann title = IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells date = 2019-06-12 keywords = IAV; IFITM3; a549; figure summary = title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. A strong IFITM3 clustering with a ring-like appearance indicating vesicle coating was observed in both IAV-infected A549 cells ( Figure 5A ) and HSAEpCs at 10 h p.i. doi = 10.3390/v11060548 id = cord-007853-5xnft6pd author = Lai, Yanni title = 3D-quantitative structure–activity relationship and antiviral effects of curcumin derivatives as potent inhibitors of influenza H1N1 neuraminidase date = 2020-04-04 keywords = IAV; curcumin summary = In the present study, we evaluated the antiviral effects of curcumin derivatives as potent inhibitors of influenza H1N1 neuraminidase based on 3D quantitative structure-activity relationship (QSAR) (Duarte et al. Confluent MDCK cell layers infected with 100 μL 100 TCID 50 IAV (H1N1) were treated with curcumin derivatives or oseltamivir carboxylate (20 mM, non-toxic concentration, data not shown) for 24 h. In this study, we used a 3D-QSAR model and docking model to investigate the inhibitory effects of curcumin derivatives against neuraminidase and influenza A/Font Monmouth/47(H1N1, FM1) in MDCK cells in vitro. We established a meaningful 3D-QSAR model (CoMFA) to study the SAR between curcumin derivatives and neuraminidase, and predicted the activity of the ligand in the test set. In addition, curcumin derivatives had different inhibitory effects on IAV neuraminidase protein, which was relative to their structures and binding models. doi = 10.1007/s12272-020-01230-5 id = cord-003888-lgutt1r9 author = Lauterbach, Sarah E. title = Assessing exhibition swine as potential disseminators of infectious disease through the detection of five respiratory pathogens at agricultural exhibitions date = 2019-09-18 keywords = IAV; exhibition summary = doi = 10.1186/s13567-019-0684-5 id = cord-028887-eseo7lyh author = Li, Chong title = Exploring heterologous prime-boost vaccination approaches to enhance influenza control in pigs date = 2020-07-09 keywords = AUT; IAV; LAIV; WIV; com summary = doi = 10.1186/s13567-020-00810-z id = cord-338070-y8zi8iz9 author = Liu, Wei title = Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib ameliorates influenza-virus-induced pneumonia in mice date = 2020-08-31 keywords = IAV; lung; olaparib summary = doi = 10.1007/s10096-020-04020-5 id = cord-102458-7sssm3zk author = Milanez-Almeida, Pedro title = Blood gene expression-based prediction of lethality after respiratory infection by influenza A virus in mice date = 2020-10-27 keywords = IAV; LD50; PR8 summary = doi = 10.1101/2020.10.27.357053 id = cord-322933-5xnxjqm5 author = Murugaiah, Valarmathy title = Collectins: Innate Immune Pattern Recognition Molecules date = 2020-03-10 keywords = IAV; MBL; bind; mannose summary = doi = 10.1007/978-981-15-1580-4_4 id = cord-355931-3mvmetuv author = Nie, Chuanxiong title = Spiky nanostructures for virus inhibition and infection prevention date = 2020-07-16 keywords = IAV; figure summary = doi = 10.1016/j.smaim.2020.07.004 id = cord-321673-v5o49ees author = Nieto-Torres, Jose L. title = Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis date = 2015-07-03 keywords = IAV; SARS summary = doi = 10.3390/v7072786 id = cord-002407-25cawzi0 author = Nogales, Aitor title = Reverse Genetics Approaches for the Development of Influenza Vaccines date = 2016-12-22 keywords = IAV; IBV; influenza; virus summary = doi = 10.3390/ijms18010020 id = cord-309381-cb80ntxs author = Nogales, Aitor title = Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans date = 2019-09-30 keywords = IAV; IFITM3; IFN; Influenza; NCR; SNP; virus summary = IAV RNAs are mainly recognized by the endosomal, membrane-associated PRR Toll-like receptors (TLRs) 3 (double-stranded RNAs, dsRNAs) or 7/8 (ssRNAs), respectively [50, 51] , by the cytoplasmic PRR retinoic acid-inducible gene I (RIG-I), which detects dsRNA and 5 -triphosphates of the negative ssRNA viral genome [50, 52] , generated during replication of multiple viruses, by the NOD-like receptor family member NOD-, LRR-and pyrin domain-containing 3 (NLRP3), which recognizes various stimuli (see below) [53] and by the absent in melanoma 2 (AIM2) protein, recognizing not well-characterized influenza stimuli [54] . Another important SNP (rs34481144) associated with risk of severe influenza in humans from the United States (US) infected with seasonal IAVs is located in the 5 -UTR of the IFITM3 gene [123, 124] . doi = 10.3390/pathogens8040168 id = cord-342691-8jcfzexy author = Ochsner, Scott A. title = Consensus transcriptional regulatory networks of coronavirus-infected human cells date = 2020-09-22 keywords = EMT; Fig; IAV; MERS; SPP; hct; sars2 summary = doi = 10.1038/s41597-020-00628-6 id = cord-286741-h3oix9zc author = Park, Mee Sook title = Animal models for the risk assessment of viral pandemic potential date = 2020-04-22 keywords = H1N1; IAV; MERS; virus summary = Focusing on the pandemic potential of viral infectious diseases, we suggest what should be assessed to prevent global catastrophes from influenza virus, Middle East respiratory syndrome coronavirus, dengue and Zika viruses. When a virus with a nonhuman origin HA and an efficient human transmissibility gets transmitted from the adaptation host swine to human (4), a pandemic might ensue (5) of IAVs, avian and swine species should be considered the natural reservoir animals, and in case of MERS-CoVs, bats and dromedary camels [32, 87, 90] . In addition to NHP and hDPP4-mouse models, rabbits might be a good candidate for MERS-CoV transmission experiments due to its camel-like receptor distribution in the upper respiratory tract (Table 2 ) [142, 150] . Human-like symptoms of MERS-CoV infection have not been reproduced in other animals than hDPP4-mice and NHPs. Starting from the distinct receptor specificities of the HA proteins between avian and human IAVs, host restriction determinants of IAVs have been documented [56] . doi = 10.1186/s42826-020-00040-6 id = cord-344093-3bniy5b5 author = Peteranderl, Christin title = The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date = 2017-03-22 keywords = IAV; IFN; TRAIL; cell; infection; type; virus summary = doi = 10.3389/fimmu.2017.00313 id = cord-347053-m5m4zgfy author = Pharo, Elizabeth A. title = Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model date = 2020-06-24 keywords = IAV; TEER; USA; cell; figure summary = doi = 10.3390/v12060679 id = cord-298458-p7rvupjo author = Schmidt, Megan E. title = The CD8 T Cell Response to Respiratory Virus Infections date = 2018-04-09 keywords = CD8; IAV; RSV summary = doi = 10.3389/fimmu.2018.00678 id = cord-339392-2ocz784l author = Sharma, Kulbhushan title = Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation date = 2011-06-15 keywords = Hsp40; IAV; PKR summary = BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. It is known that under stress conditions the expression level of Hsp40 is enhanced and its cellular localization changes from cytoplasmic to nuclear [38] , however its distribution in influenza virus infected cells was not studied. Taken together, these results suggest that during IAV infection, NP induces the dissociation of the P58 IPK -Hsp40 complex leading to an inhibition of PKR activation and downregulation of eIF2a phosphorylation. In case of influenza virus infection, viral NS1 protein is known to bind directly to PKR and inhibit its activation [20, 21] . doi = 10.1371/journal.pone.0020215 id = cord-288705-f3zqhpx1 author = Slaine, Patrick title = Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model date = 2020-10-01 keywords = Fig; IAV; UPR summary = title: Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model Selective disruption of IAV glycoprotein processing and accumulation by 6-TG and 6-TGo correlated with unfolded protein response (UPR) activation and HA accumulation could be partially restored by the chemical chaperone 4-phenylbutyrate (4PBA). Thiopurines inhibited replication of the human coronavirus OC43 (HCoV-OC43), which also correlated with UPR/ISR activation and diminished accumulation of ORF1ab and nucleocapsid (N) mRNAs and N protein, which suggests broader disruption of coronavirus gene expression in ER-derived cytoplasmic compartments. Our results suggest that 406 the effects are unlikely to be mediated through DNA or RNA incorporation of 6-TG because 1) 407 replicative stress does not specifically induce UPR; 2) among viral proteins, glycoprotein 408 accumulation and processing was preferentially disrupted; 3) messenger RNA levels of HA and 409 NA were not affected. doi = 10.1101/2020.09.30.319863 id = cord-296890-08kqtw8s author = Toh, Teck-Hock title = High Prevalence of Viral Infections Among Hospitalized Pneumonia Patients in Equatorial Sarawak, Malaysia date = 2019-02-13 keywords = IAV; Kapit; RSV; Sibu summary = Specimens were examined at our collaborating institutions with a panel of molecular assays for viral pathogens including influenza A (IAV), IBV, ICV, and IDV, human adenovirus (AdV), human enterovirus (EV), human coronavirus (CoV), respiratory syncytial virus subtype A (RSV-A) or RSV-B, and parainfluenza virus (PIV) types 1–4. One study of respiratory samples collected from children living in Kuala Lumpur under 5 years of age between 1982 and 2008 found that 26.4% of the samples were positive by immunofluorescence assays and viral cultures for viral pathogens, with a prevalence of 18.6% for respiratory syncytial virus (RSV), 3.5% for parainfluenza viruses (PIVs), 2.9% for influenza viruses, and 1.37% for adenovirus [10] . The overall objective of this study was to examine the viral etiology of and risk factors for pneumonia among patients admitted to Sibu and Kapit Hospitals between June 2017 and May 2018 and, in doing so, to assist Malaysian collaborators with setting up sustainable real-time molecular assays for viral respiratory pathogens. doi = 10.1093/ofid/ofz074 id = cord-003639-bjtxf1y8 author = Vahey, Michael D title = Influenza A virus surface proteins are organized to help penetrate host mucus date = 2019-05-14 keywords = IAV; figure; virus summary = doi = 10.7554/elife.43764 id = cord-333655-lylt7qld author = Van Breedam, Wander title = Bitter‐sweet symphony: glycan–lectin interactions in virus biology date = 2013-12-06 keywords = HIV-1; IAV; SIGN; lectin; virus summary = In sum, it appears that the dimeric lectin galectin-1 can enhance HIV-1 infection efficiency by cross-linking viral and host cell glycans and thereby promoting firmer adhesion of the virus to the target cell surface and facilitating virus-receptor interactions (Ouellet et al., 2005; Mercier et al., 2008; St-Pierre et al., 2011; Sato et al., 2012) . As has been shown for IAV, acquisition or deletion of glycosylation sites may affect crucial steps in the viral infection/replication process (e.g. receptor binding, fusion, release of newly formed virions) (Ohuchi et al., 1997; Wagner et al., 2000; Tsuchiya et al., 2002; Kim & Park, 2012) , alter the capacity of the virus to avoid induction of/recognition by virus-specific antibodies (glycan shielding) Wei et al., 2010; Wanzeck et al., 2011; Kim & Park, 2012; Job et al., 2013; Sun et al., 2013) , and modulate viral interaction with various immune system lectins (Reading et al., 2007; Vigerust et al., 2007; Reading et al., 2009; Tate et al., 2011a, b) . doi = 10.1111/1574-6976.12052 id = cord-278465-tjjkz16y author = Wille, Michelle title = Urbanization and the dynamics of RNA viruses in Mallards (Anas platyrhynchos) date = 2017-03-18 keywords = IAV; virus summary = doi = 10.1016/j.meegid.2017.03.019 id = cord-102471-dtukacm7 author = Xu, Y. title = Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission date = 2020-04-22 keywords = IAV; Nanopore; sample summary = We have recently demonstrated proof-of-principle for a direct-from-sample Nanopore metagenomic sequencing protocol for influenza viruses with 83% sensitivity and 100% specificity compared to routine clinical diagnostic testing [15] . 21.20073072 doi: medRxiv preprint Here we describe Nanopore metagenomic sequencing directly from clinical respiratory samples at a UK hospital during the 2018/19 influenza season, evaluating the applicability of this approach in a routine laboratory as a test for influenza, and investigating where further optimisation is still required before the assay can be deployed in clinical practice. We assessed the performance of this experimental protocol head-to-head with routine clinical laboratory tests, and used the influenza sequence data to investigate drug resistance, genetic diversity, and nosocomial transmission events, demonstrating the diverse benefits that can be gained from a metagenomic approach to diagnostics. In this study, we conducted Nanopore metagenomic sequencing of IAV directly from clinical respiratory samples at a UK hospital during the 2018/19 influenza season, reporting a head-to-head comparison with routine clinical diagnostic tests. doi = 10.1101/2020.04.21.20073072 id = cord-347304-1o4fb3na author = Yang, Xiaoyun title = miR‐193b represses influenza A virus infection by inhibiting Wnt/β‐catenin signalling date = 2019-01-25 keywords = IAV; Wnt; a549; cell; figure summary = Overexpression of four selected miRNAs (miR‐193b, miR‐548f‐1, miR‐1‐1, and miR‐509‐1) that down‐regulated the Wnt/β‐catenin signalling pathway reduced viral mRNA, protein levels in A/PR/8/34‐infected HEK293 cells, and progeny virus production. Because miR-193b showed greater inhibition of Wnt/β-catenin signalling than miR-193a, we tested the anti-IAV activities of miR-193b and the other miRNAs. We overexpressed each miRNA in HEK293 cells for 24 hr, infected the cells with A/PR/8/34 at a multiplicity of infection (MOI) of 0.01 for 48 hr, and determined viral mRNA and protein expression in infected cells and the titre in the culture medium. It is noteworthy that miR-509-1 inhibited the Wnt/β-catenin signalling, the second most but merely showed moderate suppression of the IAV infection, suggesting a possible offtarget effect of the miRNA. Furthermore, four miRNAs (miR-193b, miR-548f-1, miR-1-1, and miR-509-1) that down-regulated the Wnt/β-catenin signalling pathway were shown to suppress IAV replication and virus production. doi = 10.1111/cmi.13001 id = cord-307813-elom30nx author = Yip, Tsz-Fung title = Advancements in Host-Based Interventions for Influenza Treatment date = 2018-07-10 keywords = IAV; IFN; TNF; cell; infection; influenza; viral; virus summary = Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. doi = 10.3389/fimmu.2018.01547 id = cord-260452-js4nr4d8 author = Yu, Junyang title = Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection date = 2017-10-31 keywords = IAV; NLRP3; RNA; inflammasome summary = Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. IL-1β and IL-18 serve to activate myriad downstream cell responses, and orchestrate innate and adaptive immunity through MyD88/IRAK4/TRAF6-mediated NF-κB signaling and the JNK/p38 mitogen-activated protein kinase pathways (60-63), which may represent key events for the NLRP3 inflammasome-dependent antiviral defense. In BV-2 mouse microglia cells infected by Japanese encephalitis virus, the NLRP3 inflammasome induces production of IL-1β and IL-18 rapidly (within 3 h of exposure) and of TNF-α, CCL2, and IL-6 later (within 6 h after exposure) (40) ; the findings suggest that the NLRP3dependent protective inflammatory response is a very early phase innate immune response against RNA viral infection. doi = 10.3389/fimmu.2017.01420 id = cord-329680-ekxsv91t author = Yu, Yunjia title = Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/MAPK signaling pathways date = 2019-12-23 keywords = Akt; Fig; IAV summary = doi = 10.1186/s12985-019-1266-x id = cord-310004-h9ixhhzz author = Yuan, Shuofeng title = Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target date = 2020-08-28 keywords = A71; ACA; AP2M1; Fig; IAV; ZIKV summary = doi = 10.1126/sciadv.aba7910 id = cord-011438-imbpgsub author = Zhang, Yun title = Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection date = 2020-03-29 keywords = IAV; IFN; Influenza; infection; virus summary = doi = 10.3390/v12040376 id = cord-000434-ff2zadol author = Zhao, Rongmao title = Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus date = 2011-08-19 keywords = ELISA; IAV; P31 summary = The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs. Influenza A viruses (IAVs), members of the Orthomyxoviridae family, are highly contagious to a variety of avian and mammalian species. To confirm that these antibodies can recognize the HA antigen, the reactivity of the anti-peptide sera were evaluated by Western blot and ELISA against the purified HA0 protein of H1N1pdm virus. The sensitivity and specificity of peptide-ELISA versus HI test was 96.5% and 74.4%, respectively, indicating the potential of the peptide-ELISA method in detecting antibody against H1-subtype IAVs. In the present study, we identified immunodominant linear B cell epitopes on the H1N1pdm virus HA protein by a peptide scanning approach using H1N1pdm patients sera. To screen the H1-subtype specific epitopes, a set of 50 peptides spanning the amino acid sequences of the HA protein ectodomain of pandemic A/H1N1 2009 (H1N1pdm) influenza virus strain A/ California/04/2009 were synthesized. doi = 10.1371/journal.pone.0023374 id = cord-321112-w7x1dkds author = Zhao, Xuesen title = IFITM Genes, Variants, and Their Roles in the Control and Pathogenesis of Viral Infections date = 2019-01-08 keywords = IAV; IFITM3; virus summary = doi = 10.3389/fmicb.2018.03228 id = cord-291014-cfnoxhtd author = Zheng, Jian title = Immune responses in influenza A virus and human coronavirus infections: an ongoing battle between the virus and host date = 2018-02-28 keywords = IAV; MERS; SARS summary = doi = 10.1016/j.coviro.2017.11.002 id = cord-278523-djjtgbh6 author = Zhou, Bei-xian title = β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling date = 2020-06-05 keywords = Fig; IAV; IFN; rig summary = doi = 10.1038/s41401-020-0403-9 id = cord-000354-05lnj3w0 author = de Vries, Erik title = Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway date = 2011-03-31 keywords = DYNA; FCS; Fig; IAV; IND; PBS; entry summary = doi = 10.1371/journal.ppat.1001329 id = cord-006362-7d5wzb7p author = van Riel, Debby title = Influenza pathogenicity during pregnancy in women and animal models date = 2016-07-07 keywords = H1N1; IAV; influenza; pregnant summary = doi = 10.1007/s00281-016-0580-2