cord-000354-05lnj3w0	2011	
cord-000434-ff2zadol	2011	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.
cord-002407-25cawzi0	2016	
cord-002823-n55xvwkf	2018	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.
cord-003169-bdw5ke4i	2018	
cord-003498-4ct0ywnw	2019	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] .
cord-003598-m2fsrwvw	2019	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
cord-003639-bjtxf1y8	2019	
cord-003772-1345qct4	2019	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.
cord-003870-hr99dwi7	2019	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).
cord-003888-lgutt1r9	2019	
cord-004018-33zi29bg	2019	
cord-004280-c470nlie	2020	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.
cord-006362-7d5wzb7p	2016	
cord-007853-5xnft6pd	2020	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.
cord-011438-imbpgsub	2020	
cord-013174-whg64w0w	2020	
cord-028887-eseo7lyh	2020	
cord-102458-7sssm3zk	2020	
cord-102471-dtukacm7	2020	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.
cord-102586-mx534xbx	2020	
cord-255980-u0c6pg8n	2010	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.
cord-260452-js4nr4d8	2017	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.
cord-267531-tqqj4cy0	2014	
cord-272117-erzpz3c0	2018	
cord-275821-yu39aw54	2017	
cord-278465-tjjkz16y	2017	
cord-278523-djjtgbh6	2020	
cord-286741-h3oix9zc	2020	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] .
cord-288705-f3zqhpx1	2020	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.
cord-291014-cfnoxhtd	2018	
cord-291534-c6cjxq07	2013	
cord-296890-08kqtw8s	2019	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.
cord-298458-p7rvupjo	2018	
cord-300423-q2i328sz	2020	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.
cord-307148-k1uo3fxm	2020	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.
cord-307813-elom30nx	2018	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.
cord-309010-tmfm5u5h	2017	
cord-309381-cb80ntxs	2019	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] .
cord-310004-h9ixhhzz	2020	
cord-310780-0k8owwf8	2013	
cord-314825-fzba05wn	2020	
cord-321112-w7x1dkds	2019	
cord-321673-v5o49ees	2015	
cord-322933-5xnxjqm5	2020	
cord-324696-htx0ul4o	2017	
cord-325192-italbsed	2014	
cord-329680-ekxsv91t	2019	
cord-332725-2oc1yrzx	2012	
cord-333655-lylt7qld	2013	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) .
cord-335871-zieuc7vk	2020	
cord-338070-y8zi8iz9	2020	
cord-339392-2ocz784l	2011	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] .
cord-342691-8jcfzexy	2020	
cord-344093-3bniy5b5	2017	
cord-347053-m5m4zgfy	2020	
cord-347304-1o4fb3na	2019	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.
cord-355931-3mvmetuv	2020