cord-000804-0hlj6r10	2012	While the ectodomain, which is mainly formed by GP 1 , mediates binding to entry factors and receptors [87] [88] [89] [90] [91] [92] [93] [94] [95] , the transmembrane subunit GP 2 contains the fusion peptide and is presumed to mediate fusion of the viral and the cellular membrane based on similarity to EBOV GP 2 both at the amino acid and structural level [96, 97] . The IFN-inducible antiviral protein tetherin was shown to block the release of VP40-induced virus-like MARV and EBOV particles, suggesting that tetherin might act as a restriction factor for filovirus release [102, 103] . After the nucleocapsid is released into the cytoplasm of the infected cell, transcription and replication of the viral RNA genome takes place (Figure 7 ). Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections
cord-000808-pxryt8wn	2012	Since the reemergence of Ebola virus in Central Africa, the CIRMF "Emerging Viral Disease Unit" developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. As a National reference laboratory, CIRMF has the following roles: diagnosis of suspected cases during outbreaks of viral hemorrhagic fevers or severe clinical infectious syndromes; development of new methods for diagnosing such infections; surveillance of animal fatalities in reservoir or intermediate hosts; and intervention during outbreaks of unknown etiology. The Emerging Viral Diseases Unit, CIRMF, proposes forming a research partnership to study infectious diseases transmitted by animals of the tropical rain forests regions of Equatorial Africa.
cord-001831-3aonqyub	2015	Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. Research over recent decades has identified a group of virus-encoded proteins able to mediate the passage of ions and solutes across cellular membranes, termed viroporins [1, 2] . Due to these broad perturbations to host cell physiology, it is not surprising that viroporin function has been shown to assist in all stages of the virus life cycle including entry, membrane penetration, genome replication and virus egress [1, 2] . This review will summarize our understanding of these putative viroporins, describe their known functions and attempt to highlight how possible ion channel activity may aid the life cycles of these small DNA tumor viruses.
cord-001887-d6ycc8ci	2015	
cord-001972-1zisomq5	2016	These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways. Cells treated with pH1N1 had higher level of NF-kB phosphorylation and increased protein expression of NFAT and AP-1 ( Figure 3B ) relative to HIV-1 infection alone, suggesting pH1N1 infection can activate host transcription factors required for HIV-1 replication in Jurkat cells. These data indicate that pandemic influenza A (H1N1) infection can increase accumulation of CD4 protein and induce T cell signaling and activate host transcription factors required for HIV-1 replication. In conclusion, our results demonstrate that pandemic influenza A (H1N1) virus infection can induce cell death through apoptotic signaling pathways and promote HIV-1 replication through the MAPK and TCR-related signaling pathways in HIV-1-infected Jurkat cells. Pandemic influenza A (H1N1) virus infection is also able to reactivate HIV-1 replication from its state of latent infection through activating apoptosis and TCR-signaling pathways.
cord-001974-wjf3c7a7	2016	Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. The datasets went through a sequential pipeline with modules (in order) of preprocessing, computational subtraction of host sequences, low-complexity sequence removal, sequence assembly, clustering, association to metadata features, and taxonomical annotation. Associations from the shortest mode tended to have higher dispersion in the range of ORs. Furthermore, one block of clustering results using global alignment mode, alignment length based on the shortest contig, and a minimum sequence identity of 90% (c09ˆaSyG1), had an overall high range of ORs as well as the highest minimum values. The clusters are significantly associated with lowest p-values to biological features and the species annotations are described by HMP.
cord-002076-7t4d4vvo	2016	Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. Replicating-competent reporter-expressing viruses (RCREVs) are one type of artificially modified viruses that not only retain the viral genetic characteristics but also possess the new properties of the reporter genes, which represent a useful tool for quantitative analysis of viral replication and tracking viral protein transport in both living cells and animals.
cord-002185-oz7hras7	2016	In this system, 4-hydroxy-zuclomiphene appeared more potent than the Our previous findings indicated that clomiphene blocks EBOV infection by blocking entry of viral particles into the cell cytoplasm [20, 29] ; this effect appears to be at the level of fusion between the membrane of the viral particle and the limiting membrane of an Niemann-Pick disease, type C1 positive (NPC1 + ) endolysosome, the site of EBOV fusion [30] [31] [32] . Similar results were seen when comparing eight doses of clomiphene and zuclomiphene in trVLP infection ( Figure 5A ) and VLP entry ( Figure 5B ) assays. Where tested, they were equally effective to each other in two cell types and for entry mediated by three filoviral GPs. 4-hydroxy-enclomiphene, and 4-hydroxy-zuclomiphene also blocked EBOV trVLP infection and VLP entry under the 
cord-002561-7j43yic1	2017	Astroviruses within the Mamastrovirus genus are derived from numerous mammalian species in addition to humans (HAstV), including farmed species such as pigs (PAstV), sheep (OAstV), cattle (BoAstV), domesticated animals including cats (FAstV), and dogs (CaAstV), rodents and small mammals including mink (MiAstV), bats (BAstV), rats (RAstV), mice, rabbit (RabAstV), fox, marmot (HHMastV), porcupine, shrew, vole, and larger species including deer (CcAstV), monkeys, water buffalo (BufAstV), yak, camel (DcAstV), and cheetah (ChAstV) (Figure 1a,b) . Viruses from the Avastrovirus genus have been characterized from numerous farmed avian species including turkeys (TAstV), ducks (DAstV), chicken (CAstV), guineafowl (GFAstV), pigeon (PiAstV), goose, as well as wild aquatic and terrestrial birds including heron, doves, penguins, and many other species (Figure 2a) . Astrovirus strains identified from fecal samples of multiple non-human primate species from wild, captive, and peri-urban environments in Bangladesh and Cambodia reveal multiple interspecies transmission events, with viruses closely related to the VA/HMO lineage of human viruses, and non-human mammalian and avian astroviruses (Figure 1a,b) [28] .
cord-002589-xq3iq8ai	2017	To follow up these studies, we report here on (1) the investigation of PRRSV active infection (RNA in tonsil) using the same 2013 abattoir survey sample-set and (2) an analysis of the correlation of PRRSV and HEV infection in these pigs, which could be of significance for the control of both diseases and in informing farming practices for reducing HEV in the food chain. The phylogenetic trees (Figure 1 ) illustrate the genetic diversity of the ORF5 genes from the 23 samples in this study in comparison to the vaccine virus licensed in the UK at the time and 48 published reference sequences representing the different genotypes and subtypes ( Figure 1A ) and in more detail, in the context of 431 previously sequenced viruses specifically from UK pigs between 1991 and 2014 (unpublished data) ( Figure 1B ).
cord-002590-24o2viv3	2017	Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: A meta-analysis approach Antigen-specific B-cell responses to porcine reproductive and respiratory syndrome virus infection The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo Pathogenic and humoral immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) are related to viral load in acute infection Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-infected pigs The role of porcine reproductive and respiratory syndrome virus infection in immune phenotype and Th1/Th2 balance of dendritic cells Porcine reproductive and respiratory syndrome virus induces pronounced immune modulatory responses at mucosal tissues in the parental vaccine strain VR2332 infected pigs
cord-002691-synm1cyw	2017	title: PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication Results revealed that the TOR signaling pathway may have retained its activity involved in controlling cap-dependent protein translation in C6/36 cells infected by the DENV2. Results revealed that the TOR signaling pathway may have retained its activity involved in controlling cap-dependent protein translation in C6/36 cells infected by the DENV2. This suggested that the PERK signaling pathway is involved in regulating cellular protein translation when ER stress is induced by DENV2 in mosquito cells. This suggested that the PERK signaling pathway is involved in regulating cellular protein translation when ER stress is induced by DENV2 in mosquito cells. In the meantime, PERK inhibition in this study was further shown to increase MMP changes and ROS accumulation, indicating that DENV2-induced ER stress may be reduced by activating the PERK signal pathway since such cellular responses were not evidently shown in uninfected PERKi-treated cells (Figures S1-S3) .
cord-002808-84np9brx	2017	How does L2, the minor capsid protein from a non-enveloped virus, complexed with the vDNA within the lumen of intracellular vesicular compartments, interact with a variety of cytosolic sorting molecules to direct its own transport to the TGN? Given the requirement for furin in TGN localization of L2/vDNA, it is very likely that cleavage triggers a structural change that enables L2 to insert and protrude into the local membrane via the TMD to recruit cytosolic SNXs and retromer. Regardless of the precise mechanisms of L2 translocation, the minor capsid protein eventually leaves vesicular compartments and is seen along with vDNA within interphase nuclei of infected cells, localized to punctate nuclear foci called promyelocytic leukemia (PML) nuclear domains, also known as PML oncogenic domains (PODS), or ND10 bodies [108] . The L2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral DNA Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection
cord-002994-1zjrunzc	2018	Based on these alignments, we investigated the genetic properties of these different isolates circulating in West Africa, such as genome length and location of main conserved amino acid motifs previously described in mosquito-borne flaviviruses (MBFVs) with sometimes mutations which include no physicochemical properties changes [3] . The RNAz method [21] implemented in the Vienna RNA Websuite (http://rna.tbi.univie.ac.at/) [22] was used to detect thermodynamically stable and evolutionarily conserved structural RNA domains on complete non-coding regions of the 11 West African BAGV isolates characterized in this study and the isolates from Spain and CAR, because complete non-coding sequences are not currently available for the isolate from India. Here, we described location of main conserved amino acid motifs on BAGV proteins using in silico analysis of complete genome sequences of the 11 West African BAGV isolates characterized in this study and sequences from India, CAR and Spain.
cord-003130-p2h8p5bm	2018	There are more than 70 viruses in the genus flavivirus, and they are transmitted by arthropods such as mosquitoes (dengue virus (DENV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV) and ticks (tick-borne encephalitis virus (TBEV), Langat virus (LGTV), Kyasanur forest disease virus (KFDV), Omsk hemorrhagic fever virus (OHFV), Powassan virus (POWV), and Louping-ill virus (LIV)) [1] [2] [3] [4] [5] . Two other ISGs which have been shown to be antivirally active against TBEV are virus inhibitory protein endoplasmic reticulum associated interferon inducible (viperin) and tripartite motif-79α (TRIM79α). The role of interferon in tick-borne encephalitis virus-infected l cells. A functional toll-like receptor 3 gene (tlr3) may be a risk factor for tick-borne encephalitis virus (tbev) infection Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection
cord-003284-hjx2d5rq	2018	Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. To analyze the genetic stability of the recombinant ZIKV harboring the point mutation A175V in the coding region of the NS2A protein (rZIKV-RGN-mNS2A), total RNA was purified from Vero cells infected with viruses from passage 1 (P1) to passage 5 (P5) using the RNeasy minikit (Qiagen), according to the manufacturer''s specifications. To investigate whether the reduced RNA synthesis of rZIKV-RGN-mNS2A in Vero cells could result in viral attenuation in vivo, the ability of the mutant virus to induce pathogenesis was analyzed in A129 mice and compared with that of the parental rZIKV-RGN ( Figure 6 ).
cord-003334-ion97n4b	2018	Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Considering that we observed a significant reduction in the IBV induced morbidity and mortality of in ovo CpG ODN pre-treated birds correlating with varying degrees of increased macrophages, CD4+, and CD8α+ T cells in the tracheal and lung tissues, we needed to further elucidate the mechanisms by which these immune cells were efficiently recruited.
cord-003407-f5v3hhr8	2018	Thus, RC''s anti-HCV activity appeared strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. Viruses 2018, 10, x FOR PEER REVIEW 6 of 12 strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. To further characterize the mechanism(s) underlying RC''s anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. To further characterize the mechanism(s) underlying RC''s anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry.
cord-003453-p2buyrcj	2019	In this study, we tested the activity of the natural compounds berberine and emodin for their ability to inhibit ZIKV infection. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection.
cord-003516-l1lq8yga	2019	title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations A signature of these "old" HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the "new" HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Recent isolates are recombinants containing this HAdV replication motif [1] , presumably permitting an expansion of the virus range into the immune-naïve populations [5] [6] [7] [21] [22] [23] , and should be noted as a molecular evolution example of a post-zoonotic, host-adaptation of a "novel" and "emergent" human pathogen.
cord-003586-afnto2tz	2019	We identified host cellular proteins that interact with Z proteins of both viruses by using a high throughput yeast two-hybrid (HT-Y2H) screening protocol in which AH109 yeast cells were transformed with a Y2H vector encoding the Z protein of LASV or MOPV fused to the GAL4-BD domain (viral bait). Y2H screens allowed us to identify, among others, two known autophagy adaptors, namely NDP52 and TAX1BP1, which have been shown to interact with the Z protein of MOPV, but not LASV (Table 1) . Overall, these results suggest that NDP52 and TAX1BP1 are not involved in the production of infectious virus for either MOPV or LASV in HeLa cells. These results were unexpected and suggest that autophagy adaptors could play a role during LASV or MOPV infection that does not affect the viral fitness in the cell lines we used.
cord-003646-kjkuet78	2019	We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. In mice, ChAdOx1 vaccines candidates expressing sCHIKV antigens are able to induce strong humoral and cellular responses upon a single and non-adjuvanted immunisation approach. Finally, whilst durability of humoral responses was achieved upon a single immunisation, MVA vaccines expressing sCHIKV were produced to be used as an alternative heterologous booster regime (ChAdOx1/MVA), in order to increase neutralising antibody titres. In addition, a western blot was performed using a monoclonal antibody against CHIKV E1 (Figure 3d ); we detected a specific band in the positive control E1 protein (lane 9), as well as a 55 kDa band in all the supernatant fractions from both ChAdOx1 sCHIKV-and ChAdOx1 sCHIKV ∆C-transduced cells.
cord-003697-vmmlxr0o	2019	
cord-003761-ikni2acz	2019	In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. In particular, the 2B protein may change the Ca 2+ concentration to regulate autophagy and apoptosiswhich are distinct cell death mechanisms controlled by the virus to effectively evade the host immunity, thereby promoting viral replication and release [48] [49] [50] [51] [52] . Thus, the main points of focus for research on the structure and function of the 2B protein toward ultimate drug development are: (1) mechanism of increasing membrane permeability to disturb the ion balance, (2) regulation of autophagy and apoptosis, (3) inhibition of the host immune response, and (4) promotion of viral replication and release.
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-003775-1axsebya	2019	Herein, we report the isolation, nearly complete genome sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. In this study, we report the isolation, nearly complete genomic sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. Phylogenetic analyses suggest that HYPV belongs to the Chordopoxvirinae subfamily, revealing the highest similarity (85%) with Eptesipoxvirus (EPTV) detected from the microbat Eptesicus fuscus in WA, USA in 2011, which is associated with bat necrosuppurative osteomyelitis in multiple joints. For the nearly complete viral genome sequencing, BLAST analysis revealed the highest nucleotide identity (85%) to the Eptesipoxvirus (EPTV) strain "Washington", a member of the Chordopoxvirinae subfamily identified in microbats in the USA ( Table 2 ). To conclude, a new poxvirus, HYPV, was detected in bats in Europe and its viral ecology and disease associations should be investigated further.
cord-003807-e2txo10z	2019	Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells. Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells. Rana grylio virus (RGV) and Andrias davidianus ranavirus (ADRV) are ranaviruses isolated from diseased pig frogs R. Furthermore, since ranavirus viral envelope proteins [38] [39] [40] [45] [46] [47] [48] are likely involved in the initial interaction between virus and host, we examined the ability of RGV-53R and its ADRV homolog, ADVR-58L, to bind heparin-Sepharose beads. The effect of heparin on virus infection was tested by monitoring viral plaque formation following incubation of ADRV and RGV in the presence of increasing concentrations of heparin.
cord-003859-k8wfyj9b	2019	title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to evaluate and compare the diagnostic performance of EBOV IgG-indirect ELISAs based on antigens produced by classical virological and recombinant protein expression methods using human serum panels from EBOV non-infected and EBOV infected humans.
cord-003861-qeao4ghg	2019	To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. To better understand the role of correlated evolution and positive selection in the evolutionary dynamics of viruses infecting humans, we constructed a nearly exhaustive viral data set spanning all dsDNA, dsRNA, ssRNA, and ssDNA viruses deposited in GenBank (as of August 2017), and conducted an extensive survey of correlated evolution and diversifying selection in these viruses, asking more specifically about the prevalence of these two processes in each viral type, independently or jointly, with the specific hypothesis that the genes affected by both processes encode functions that are most critical to each viral life cycle.
cord-003865-24lz9tf1	2019	To evaluate the antiviral effects of the three drugs of Nitazoxanide, Closantel Sodium and Closantel, F81 cells were seeded in 6-well plates at 7.5 × 10 5 cells per well and pretreated with the 3 drugs at a final concentrations of 5 µM, 10 µM, and 20 µM, respectively, for 1 h, then treated cells were infected with CPV at MOI of 0.076 as described above. As mentioned above, the identified drugs Nitazoxanide, Closantel Sodium, and Closantel can reduce the copy numbers of CPV viral DNA to 0.07%, 24.04%, and 20.83%, respectively, compared with the 0.1% DMSO-treated control ( Figure 3) . Our CPE-based screening assay showed that the percentage CPE inhibition of Oseltamivir and Cidofovir were 2.13 ± 2.41 and −1.28 ± 1.03 (Table S1 ), respectively, and that these two drugs had no anti-CPV effects on F81 cells.
cord-003915-kje8lvgl	2019	As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects. In addition, we showed that JcDV early infection results in (i) an arrest of N-Acetylglucosamine (GlcNAc) secretion by epithelial cells associated with a disorganization of the PM structure mimicking the effect of chitin-binding plant lectin; (ii) substantial changes in the expression of gut genes, which may also contribute to an early gut dysfunction and participate to viral pathogenesis. Results presented here show that JcDV capsids display carbohydrate-binding properties that insure recognition of the peritrophic matrix and determines caterpillars oral infection.
cord-003917-bswndfvk	2019	Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . Interestingly, evidence collected in animal studies, in the epidemiological analysis of transmission chains, and in the most recent Ebola outbreaks suggests that EBOV may be able to cause primary pulmonary infection.
cord-003961-gs75ebo4	2019	The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). The available evidence suggests that naked and quasienveloped HEV particles use different mechanisms for cell entry, and that entry of eHEV requires lysosomal degradation of the viral membrane. ORF3 protein of hepatitis E virus is essential for virion release from infected cells
cord-003962-lg6gvgwt	2019	The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. The results showed that the mutations of the residues D84 and E90 (e.g., D84N, D84R, E90R, E90Q, etc.) did not have much effect on PLP2 DUB activity, as the corresponding mutants could efficiently cleave K63 or K48 polyubiquitin chains into monomers ( Figure 4A , lanes 3, 4, 7, and 8).
cord-004018-33zi29bg	2019	We used a newly-developed aptamer-based multiplexed technique (SOMAscan(®)) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems. We found that the culture-adapted PR8 strain had an overall activation of immune molecules, the mild seasonal and pdm09 human strains had little effect upon the molecules targeted by the SOMA panel, and the avian H5N1 and H7N9 strains, that are much more pathogenic in humans, had the most dramatic proteomic responses, these upregulating a few tested molecules, but inhibiting many more key cellular processes. Quantitative proteomic analyses of influenza virus-infected cultured human lung cells Quantitative analysis of cellular proteome alterations in human influenza A virus-infected mammalian cell lines
cord-004020-qtwcbn7m	2019	A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Gossypol-treated ZIKV was incubated with Vero E6 cells at 37 • C for 1 h in the presence of DMEM containing serial dilutions of each of the other three natural products identified, such as curcumin, digitonin, and conessine, or anti-ZIKV compound control (bortezomib). Based on Table 1 , four "hit" natural products, including gossypol, curcumin, digitonin, and conessine ( Figure 2A -D), were selected, since they demonstrated inhibitory activity against ZIKV infection with no obvious cytotoxicity in Vero E6 cells when observed under a microscope. Since gossypol demonstrated the highest antiviral activity individually against all ZIKV strains tested, we next investigated the potential combinatorial effects of the combination of gossypol with three other natural products identified, namely curcumin, digitonin, and conessine, as well as anti-ZIKV compound control (bortezomib).
cord-004022-cr0zskcw	2019	The packaging cells carrying the recombinant plasmid encoding the viral structural proteins are transfected with DNA-launched replicons and then self-replicate viral subgenomes and express all viral proteins, allowing viral assembly and release as SRIPs. Several flavivirus, replicon-based SRIPs, including JEV, dengue virus, West Nile virus, and tick-borne encephalitis virus have been generated and demonstrated as safer vaccine candidates [15] [16] [17] . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) .
cord-004334-y1fcw1dj	2019	Antigen-specific IgG responses induced by immunization with the vaccine candidates were analyzed by enzyme-linked immunosorbent assay (ELISA) using purified soluble recombinant NiV glycoprotein G expressed in mammalian HEK293 cells. IFNAR−/− mice on a C57BL/6 background (MHC I = H2-Db/H2-Kb (H2-b) and MHC II = H2-IAb) were immunized twice with the MVA-NiVsG candidate vaccine via the intraperitoneal (i.p.) route, and splenocytes were prepared 8 days after the final inoculation, CD4 and CD8 T cells were purified and restimulated with overlapping 15mer peptides corresponding to the NiV-G protein. IFNAR−/− mice on a C57BL/6 background (MHC I = H2-Db/H2-Kb (H2-b) and MHC II = H2-IAb) were immunized twice with the MVA-NiVsG candidate vaccine via the intraperitoneal (i.p.) route, and splenocytes were prepared 8 days after the final inoculation, CD4 and CD8 T cells were purified and restimulated with overlapping 15mer peptides corresponding to the NiV-G protein.
cord-004335-bw3tziup	2019	
cord-004337-jtaz1gdp	2020	title: A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses Here, we report that production of SUDV VLPs has been accomplished in insect cells by the co-infection with recombinant baculoviruses rBV-GP-GP and rBV-VP40-VP40, and evaluate the ability of SUDV-VLPs to induce SUDV-specific humoral and cellular immune responses in vaccinated mice. To detect a SUDV-VLP-induced humoral immune response in vaccinated BALB/c mice, indirect ELISA and virus neutralization assay were performed to evaluate the production of SUDV GP-specific antibodies and neutralizing antibodies. Analysis of SUDV-VLP-induced specific IgG antibody response by indirect ELISA at two weeks after every immunization of vaccinated mice (C). Moreover, our study revealed that the B cells of mice of the group vaccinated with SUDV VLPs mixed with an ISA 201 adjuvant were activated at one week after the primary immunization (Figure 7 ).
cord-004507-ezuyjcxs	2020	The study provided complete genome sequences for nine Letea virus strains and new information about orbivirus diversity, host range, ecology and evolution. The phylogenetic clustering of Orbivirus members results in clades indicating their putative or potential arthropod vectors: Culicoidesor sand fly-borne (C/SBOV), mosquito-borne (MBOV) and tick-borne orbiviruses (TBOV) [9] . Evolutionary relationship of LEAV with representative members of the Orbivirus genus were analyzed by inferring phylogenetic trees with amino acid and nucleotide ORF sequences of conserved genes encoding the polymerase (VP1), the subcore shell protein T2 (VP2/VP3) and the major core surface protein T13 (VP7) [5, 6] . Inclusion and demarcation of species within the Orbivirus genus considers several criteria, such as sequence identity of segments encoding the polymerase (VP1) and major subcore shell protein T2, gene reassortment between close strains, high levels of serological cross-reactivity against conserved antigens like the T13 protein, conservation of UTR terminal nucleotides, range of hosts and vectors or the clinical signs associated with orbivirus infection [1] .
cord-004508-ok3px98z	2020	Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress. In a hypothesis-driven approach, an online available microarray data set of quadruplicates of non-infected DH82 and DH82Ond pi cells (ArrayExpress; http://www.ebi.ac.uk/arrayexpress; accession number E-MTAB-3942 [11, 44] ) was investigated for differentially expressed genes related to ROS production and scavenging, ER-stress and HIF-1α pathway, with a special focus on the angiogenic downstream targets of the latter.
cord-004509-jkzqmkz6	2020	In conclusion, Lyoph-P&P holds several advantages over extemporaneously preparer liquid formulation that merit to be considered when a novel real-time molecular assay is implemented in a laboratory in charge of routine diagnostic activity. Selected assays target two emerging viruses that are listed on the blueprint of the WHO as to be considered for preparedness and response actions [5] : chikungunya virus (CHIKV), a single-stranded positive-sense RNA alphavirus, and Rift Valley fever phlebovirus (RVFV), a tri-segmented, single-stranded negative-sense RNA phlebovirus. Detection of CHIKV RNA using Lyoph-P&P provides results in clinical samples that are at least equal and often better than those obtained with the extemporaneously prepared liquid formulation used as reference. Indeed, at laboratory level, it is likely that one or two different formats (number of tests per vial) will be either prepared or ordered; as a consequence, the time during which rehydrated material can be stored without affecting the expected performances of the assay is a key factor.
cord-004510-cbutpjre	2020	
cord-009399-6zpkpdzu	2020	Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Some studies suggest that IFITM proteins may suppress the entry of viruses by inhibiting the hemifusion of viral membrane and host cell membranes [15] or restricting the formation of fusion pores following virus-endosome hemifusion [16] . Alanine scanning and site-directed mutations found that KRRK basic residues were key for the restriction of IFITM proteins on ZIKV and DENV. Significantly, we found that IFITM1 can restrict the release of ZIKV from endosome to cytosol to prevent the entry of viral particles into host cells, which was associated with its inhibition on organelles acidification.
cord-011435-x73foqu7	2020	title: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. In contrast to the transcriptional pathway, nt-Irf3 in virus-infected cells functions as a chaperone protein by translocating the pro-apoptotic protein BCL2-associated X (BAX) to the mitochondria, thereby causing apoptotic cell death, which we named RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA) ( Figure 1A ) [7] [8] [9] [10] [11] [12] [13] . We validated these results by immunoblot analyses, which demonstrate that doxorubicin treatment inhibited the expression of VSV-G protein, a viral envelope glycoprotein as well as the virus-encoded GFP ( Figure 3B ). We validated these results by immunoblot analyses, which demonstrate that doxorubicin treatment inhibited the expression of VSV-G protein, a viral envelope glycoprotein as well as the virus-encoded GFP ( Figure 3B ).
cord-011436-ud35mf5l	2020	It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. To further characterize the role of IFN-λ in RABV infection in the mouse model, recombinant RABVs (rRABVs) expressing murine IFN-λ2 or IFN-λ3, designated as rB2c-IFNλ2 and rB2c-IFNλ3 respectively, were constructed as shown in Figure 2A , and rescued as described previously [27] . To further investigate whether IFN-λ restricts RABV infection in vivo, groups of five-week-old female BALB/c mice were mock-infected with DMEM or inoculated with B2c, rB2c-IFNλ2, or rB2c-IFNλ3 by different routes. Expression of neuronal CXCL10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines and cytokines, and enhancement of blood-brain barrier permeability
cord-011438-imbpgsub	2020	Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. In the current review, we present a general description on recent work regarding different host cells and molecules facilitating antiviral defenses against IAV infection and how IAVs antagonize host immune responses. Host innate immunity, including phagocytic cells, interferons (IFNs), proinflammatory cytokines, etc., applies multiple mechanisms in defending IAV infection [105] . Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: Implications of a novel interaction between nucleoprotein and host protein Clusterin Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production The human interferon-induced MxA protein inhibits early stages of influenza A virus infection by retaining the incoming viral genome in the cytoplasm Cell death regulation during influenza A virus infection by matrix (M1) protein: A model of viral control over the cellular survival pathway
cord-011635-vosu7y6j	2020	This review summarizes the contribution of a newly described cell type, group 2 innate lymphoid cells (ILC2), and epithelial-derived alarmin proteins that activate ILC2, including IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and high mobility group box 1 (HMGB1). Furthermore, the epithelial-derived cytokines interleukin-33 (IL-33), interleukin-25 (IL-25), and thymic stromal lymphopoietin (TSLP), as well as the innate immune cell-derived cytokine high mobility group box 1 (HMGB1), activate and induce ILC2 function, thereby promoting the progression of type 2-mediated pulmonary diseases ( Figure 1 ) [59] [60] [61] [62] [63] [64] . These alarmin proteins released from RSV-infected epithelial cells can activate group 2 innate lymphoid cells (ILC2) to produce the type 2 cytokines IL-5 and IL-13. These alarmin proteins released from RSV-infected epithelial cells can activate group 2 innate lymphoid cells (ILC2) to produce the type 2 cytokines IL-5 and IL-13. Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection
cord-012418-6ralcn8p	2020	Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ).
cord-012420-llh22iq2	2020	Interestingly, non-pathogenic OW Mopeia virus (MOPV), a close genetic relative to LASV, induces a strong initial IFN and cytokine response in infected moDCs and macrophages leading to a sustained T cell activation and immune response [67, 68] . Similar to NP, interaction of arenavirus Z proteins with RIG-I prevents further binding to MAVS and therefore inhibits the production of IFN-β and reduces antiviral host immune responses. Although the inhibition of RIG-I signalling by highly pathogenic arenaviruses in vitro suggests that there should be limited IFN1 response, it is notable that in vivo infection with some of these viruses (LCMV, JUNV) induces high levels of IFN1, ISGs and cytokines suggesting that this strategy is not completely effective or is widely varied in cell type and differs from host to host [134, 135, 186] .
cord-012497-n5pu1yeu	2020	Finally, we sought to understand the in vivo role of STAT2 by infecting hSTAT2 knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. Mouse models for HMPV have been developed, but mice are only semi-permissive for HMPV, requiring a high viral inoculum for productive in vivo infection ( [25] and unpublished observations), which may be due to species differences in the innate immune proteins antagonized by the virus. To better understand the global consequences of substituting human STAT2 into mice in vivo, we performed multiplex cytokine analysis on lung homogenates of HMPV-infected hSTAT2 KI and WT mice at day five after high-dose inoculation, as day five represents a time point that bridges innate and adaptive immunity.
cord-012845-so2umdlt	2020	
cord-012909-o6t2srim	2020	
cord-013174-whg64w0w	2020	In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. In pigs, circulation of IAV, so-called swine influenza A virus (swIAV), is currently mainly limited to three different subtypes including H1N1, H1N2 and H3N2 [5] [6] [7] . In the phylogenetic analysis, the HA sequences of pig ID 250, obtained at weeks 4 and 8 were located in the same cluster and were~0.5% (9/1701) divergent at the nucleotide level and < 1% (5/566) divergent at the amino acid level. Comparison of amino acid sequences of neuraminidase (NA) antigenic sites of pig ID 380 sampled at week 5 and week 22 from the pig herd.
cord-013177-whd0znan	2020	Novel posa-like viral genomes were first identified in swine fecal samples using metagenomics and were designated as unclassified viruses in the order Picornavirales. These posa-like viruses have undergone a complex evolutionary process, and have a wide geographic distribution, complex host spectrum, deep phylogenetic divergence, and diverse genomic organizations. Novel posa-like virus genomes were first identified in swine fecal samples using metagenomics and were assigned as unclassified viruses to the order Picornavirales [12] . Further reports of novel posaviruses with low amino acid sequence identity revealed novel genomic organization features and phylogenetic characteristics of posa-like viruses [15, 16] . Due to the low genomic sequence similarity between the husavirus and unclassified posa-like viruses in Picornavirales, it was difficult to perform a phylogenetic analysis at the full-length genome level. Posa-like viruses identified in previous reports and in the present study formed a single group and clustered with the genomes of family Marnaviridae (Figure 4) .
cord-013178-li1x1m25	2020	title: The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs. The Porcine circovirus (PCV) is a small virus and contains closed circular single-stranded DNA [1] . For these purposes, this study used the commercial capsid antigen-ELISA and homemade ORF3 protein-ELISA (anti-N1 polyclonal antibodies and mAb 7D3 based) to detect viral proteins in pig blood.
cord-252142-aqwlcs9g	2012	Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The inhibitory effect of lectins on hPIV-2 entry into the cells and replication in the cells was analyzed using a recombinant green fluorescence protein-expressing hPIV-2 without matrix (M) protein (rghPIV-2ΔM) [9] . RNA was prepared from the lectin-treated infected cells at four days post infection, and virus-synthesized RNA was analyzed using hPIV-2 specific primers by polymerase chain reaction (PCR). These results indicated that the lectins bound to the cell surface receptors, and largely prevented the binding of hPIV-2 to the cells non-specifically.
cord-252466-usrpodjx	2012	
cord-253282-zwl0safn	2013	In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. Here, analyses using synonymous protein coding mutations demonstrate that the region of the genome that harbors the frameshift signal affects the regulation of genomic and subgenomic RNA production without altering protein sequence. Here we describe deletion and mutagenesis experiments with a dual luciferase reporter to show that the effect the sequence between stems 1 and 2 has on frameshifting efficiency is due to structural changes those mutations cause in the pseudoknot. Similar to previously described viruses containing mutations in the slippery site of the frameshift signal [7] , here we show that mutations to the SARS-CoV frameshift stimulating mRNA pseudoknot can also affect the production of viral genomic RNA.
cord-253629-5aofwe1w	2020	
cord-254181-nquozaxt	2019	To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. To elucidate the target tissues of FeMV-GT2 we established protocols for the isolation of primary feline cells from various organs of cats (see section 2.2.) Experimental in vitro infection was performed using the LLC-MK2-adapted FeMV-GT2-Gordon strain. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above.
cord-254250-l0v602x9	2020	title: A Novel RNA Virus, Macrobrachium rosenbergii Golda Virus (MrGV), Linked to Mass Mortalities of the Larval Giant Freshwater Prawn in Bangladesh De novo virus assembly revealed a 29 kb single-stranded positive-sense RNA virus with similarities in key protein motif sequences to yellow head virus (YHV), an RNA virus that causes mass mortalities in marine shrimp aquaculture, and other viruses in the Nidovirales order. rnaSPAdes assembly of combined libraries produced 38,826 contigs; 23 contigs, of average length 4560 bp, had similarity in protein sequence to YHV or gill-associated virus (GAV), but when the trimmed reads were aligned against the YHV genome (accession number GCA_003972805.1), no alignment was seen. rosenbergii were negative: MrNV and XSV, the causative agents of white tail disease [9, 10] ; MrTV, a virus associated with mass larval mortalities in China [15] , Spiroplasma eriocheiris [8] , and WSSV-shown to be able to infect M.
cord-254596-wsmnlnlk	2020	
cord-255607-dbexsugq	2020	
cord-255683-2eq24jth	2010	Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. To find whether the activity of the antibodies is related to antibody size and how the viral infection could be affected by cross-linking of HIV-1 Envs, we generated a single-chain Fv fragment (scFv) (scFv m19) of m19 and a human IgG1 Fc-fusion protein (m19Fc) of scFv m19; m19 was selected for further characterization because its light chain was relatively less divergent from the germline ( Figure 1b) and was the only one which did not contain any somatic mutations in the CDR3 of the light chain.
cord-256370-cz88t29n	2016	
cord-256713-tlluxd11	2011	[15] show that for a class of networks known as random intersection graphs in which individuals belong to one or more overlapping groups and groups form fully connected cliques, an increase in clustering reduces the epidemic threshold, that is, major outbreaks may occur at lower levels of transmissibility in highly clustered networks. They demonstrate that a rewiring of random intersection graphs that preserves the degree sequence but decreases clustering produces networks with similarly lowered epidemic thresholds and even smaller mean outbreak sizes. From a statistical point of view, these results indicate that even with full data from a particular epidemic outbreak, such as complete knowledge of the transmission tree, it is unlikely that the level of clustering in the underlying contact network could be accurately inferred independently of the degree distribution.
cord-256924-c7ftvgio	2012	Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. Recently three new HCoVs, all detected in patients with ARIs were described; the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, HCoV-NL63 in 2004 and HCoV-HKU1 in 2005 [16] [17] [18] . Our retrospective study also observed that clinical features and the average severity scores from patients with HCoV were very close to those from a similarly aged set of children who were positive for HRSV. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method Frequent detection of human coronaviruses in clinical specimens from patients with respiratory tract infection by use of a novel real-time reverse-transcription polymerase chain reaction
cord-257052-cik2wmlk	2018	title: Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling. Ectopically expressed NS1 inhibited interferon-β promoter activity that was induced by RIG-IN as determined by the luciferase assays in HEK293T cells, confirming that NS1 itself is capable of inhibiting RIG-I-mediated antiviral signaling ( Figure 1A ). Ectopically expressed NS1 inhibited interferon-β promoter activity that was induced by RIG-IN as determined by the luciferase assays in HEK293T cells, confirming that NS1 itself is capable of inhibiting RIG-I-mediated antiviral signaling ( Figure 1A ). These results suggest that RSV NS1 expression diminishes the interaction between RIG-I and MAVS by interfering with TRIM25-mediated RIG-I ubiquitination. These results indicate that inhibition of TRIM25-mediated RIG-I ubiquitination by NS1 contributes to the suppression of RIG-I signaling, at least in part.
cord-257539-01s21vh0	2016	Immunofluorescence staining corroborated these results ( Figure 1B ) and additionally, chloroquine decreased the production of infectious ( Figure 1C ) and total ( Figure 1D ) virus particles, including defective viral particles, by ZIKV-infected cells. Incubation of Vero cells with chloroquine at 0 h postinfection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. Incubation of Vero cells with chloroquine at 0 h post-infection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ).
cord-257665-12gyrmh2	2020	We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists [3] , as this represents an important first step in curbing the spread of the new virus to other parts of the world.
cord-257913-uf9sx5qi	2009	Alternatively, one can establish whether rhesus macaques that are in close contact to humans have experienced a natural HCoV-NL63 infection by investigating the NL63-directed antibody titers in time. In the current study we use the kinetics of the antibody response to HCoV-NL63 to determine whether rhesus macaques encounter natural infections with HCoV-NL63, or related coronaviruses. The first indication of infections with HCoV-NL63-like viruses in rhesus macaques was found when we tested 32 serum samples of 32 monkeys (Table 1 and Figure 1 ). Longitudinal serum samples were available of three rhesus macaques with the highest antibody levels to HCoV-NL63 (numbers 5, 10 and 17). A well-designed follow up through the years with serum and respiratory samples collected on a regular basis would be sufficient to unravel the potential of the human respiratory viruses to infect rhesus macaques. We show here that there are clear signs that Rhesus macaques acquire natural infections with HCoV-NL63, or a serologically very closely related coronavirus.
cord-258323-vdeffy4l	2019	To detect expression of inflammasomes and complement components in MERS-CoV-infected THP-1 differentiated macrophages and hDPP4-Tg mice, 2 µg of total RNA from cells or the lung of mice we used as template for first-strand cDNA synthesis. IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). These results suggest that complement inhibition decreased the expression of pyroptosis indicators, IL-1β and caspase-1, in mice infected with MERS-CoV. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages.
cord-258536-qnn9hp8e	2017	The nsp proteins interfere with the host defenses but also induce the formation of double-membrane vesicles (DMVs) and convoluted membranes, on which they collectively form the replication-transcription complexes (RTCs) [19, 20] (Figure 2 , steps 2, 3, and 4). These complexes mediate the synthesis of the genomic RNA and a nested set of subgenomic RNAs that directs the translation of the structural proteins (the nucleocapsid N protein, the membrane M protein, the envelope E protein and the spike S protein) and some accessory proteins, like the hemagglutinin esterase in the case of Severe Acute Respiratory Syndrome (SARS)-CoV or Mouse Hepatitis Virus (MHV) [21] [22] [23] (Figure 2 , steps 5 and 6). Infected cells displayed the presence of a higher number of autophagosome-like double-membrane vesicles, an accumulation of green fluorescent protein (GFP)-LC3-positive puncta and higher levels of lipidated LC3, indicating an induction of autophagy [57] .
cord-258684-lq4knxgf	2020	
cord-259237-aty0vrat	2016	One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. The remaining Man residues are cleaved by the Golgi mannosidases, and the glycan remolding process is continued through the remainder of the N-glycosylation pathway, which generates functional glycoproteins that are delivered to the cell surface ( Figure 1B ). As introduced earlier, the UPR utilizes three different mechanisms to alleviate ER stress: reducing global protein translation, increasing the ER folding capacity, and enhancing ERAD by activating the PERK, ATF6, or IRE1-XBP1 pathways, respectively. ERManI also targets the terminally misfolded human alpha1-antitrypsin variant null (Hong Kong) (NHK) for degradation via ERAD, but neither its catalytic activity nor its catalytic domain is required for this degradation, suggesting that different mechanisms are involved in HIV-1 Env and NHK degradation [152] . The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway
cord-259273-bh5csogu	2012	mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. A cost effective approach was adopted in June 2009, to only test specimens negative for both influenza A and B by either singleplex or multiplex real time PCR assays using the Respiratory Virus Panel (RVP) classic assay, a multiplexed assay which detects multiple respiratory viral pathogens including FLUA, FLUB, PIV, ERV, ADV, 4 types of CRV, RSV, and hMPV [15] . In this study we used DIAL to select specimen-based data and investigated the proportions of mono vs mixed infections for hMPV as compared to ADV, CRV, ERV, PIV and RSV for a period of three years, 1 July 2009 to 30 June 2012.
cord-259658-rgrt6e6r	2019	
cord-259916-gr6v098c	2016	
cord-260431-eksl7pp8	2014	In the present study, we used molecular methods, virus isolation, TEM examination and an animal challenge experiment to diagnose the cause of death of the South China tiger, and for the first time, we confirmed the infection with FHV-1 in the captive tiger population in China. The phylogenetic tree based on the TK gene sequences showed that the isolate investigated in this study, was closely related to the ten isolates of FHV-1 ( Figure 2 ), a result consistent with the alignment analysis. By PCR/RT-PCR, the only virus detected in the trachea homogenates was FHV-1, which was confirmed afterwards by virus isolation, the TEM examination of cell cultures showing CPE, and a challenge experiment in cats. In this study, the authors described the first occurrence of feline herpesvirus type 1 (FHV-1) in a South China tiger in China.
cord-260476-whfyczcj	2017	
cord-260705-huyyw5z6	2012	During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intraand intercellular transportation. In plant cells, both RNA and DNA viruses are associated with large inclusions detected in the cytoplasm and nucleus, however, their role in virus propagation or oppositely in virus restraint is less investigated than in infected mammalian cells. In general, mammalian and plant viruses make use of aggregates as scaffolds for anchoring the replication complex, increasing the local concentration of viral and host components required for replication and assembly, and shielding the process of replication from host defense.
cord-261417-4pf5nsw2	2017	Why the virus prefers to use these snRNAs as targets has yet to be experimentally established, but it has been proposed that the selective de-capping of U1 and U2 RNAs in combination with the binding of the viral NS1 protein to U6 snRNA may serve to inhibit host pre-mRNA splicing [66] . The folding of the TAR hairpin is key to the regulation of HIV-1 transcription [94] as it is used as a scaffold to recruit essential transcription factors, including the 86-101 amino acid (aa) viral trans-activator protein (Tat) [83] ( Figure 3C ). Interestingly, the human T-lymphotropic virus type 1 transcriptional activator Tax also utilizes P-TEFb for viral transcription and displaces P-TEFb from 7SK snRNP through binding CycT1 [101, 102] , suggesting that P-TEFb liberation from 7SK snRNP could be a common theme developed by different viruses to support their replication in host cells.
cord-262434-q4tk96tq	2014	Finally, we speculate on the possible consequences and potential research avenues opened following this marrying of a pathogen of great historical and contemporary importance with an ancient host that has an apparently peculiar relationship with viruses; a fascinating and likely fruitful meeting whose study will be facilitated by recent technological advances and a heightened interest in bat virology. Similarly, testing the in vitro host range of isolated viruses such as Eptesipox virus would help inform whether human and further animal cell lines are permissive for infection (i.e., that they contain the necessary host factors to support infection and do not contain antiviral components that restrict infection). Further field (in situ), in vitro and in silico studies could elucidate the possible coevolution, cross species infections and mechanisms of host range restriction of bat poxviruses, the implications of which are relevant for bat ecologists, virologists and emerging infectious disease specialists (including those with a specific interest in bats) alike.
cord-262499-68vmdqky	2020	We evaluated the use of commercial Simplexa™ COVID-19 Direct assay on OF samples from hospitalized COVID-19 patients, for identification of SARS-CoV-2 RNA, duration of viral shedding, and determining the assay specificity and sensitivity on OF samples compared to NPS and BAL samples. The first performance evaluation on clinical specimen was done by testing 41 consecutive OF samples, including 9 samples from SARS-CoV-2-negative patients, with the Simplexa™ COVID-19 Direct assay and comparing results with that obtained using RT-PCR method established by Corman VM. The performance of Simplexa™ COVID-19 Direct assays on clinical specimens was further established by testing in parallel NPS and OF samples for the presence of SARS-CoV-2 RNA. The performance of Simplexa™ COVID-19 Direct assays on clinical specimens was further established by testing in parallel NPS and OF samples for the presence of SARS-CoV-2 RNA. Second, results from testing on paired OF, NPS and BAL samples by Simplexa™ COVID-19 Direct assay showed almost perfect concordance for virus detection, and high correlation of Ct values.
cord-263142-o8qbqxhx	2018	We examined blood and buccal swab specimens of domestic cats in Brazil for detection and quantification of each feline virus to evaluate their potential association with disease and transmissibility in animals with single or multiple retroviral infections. Buccal swab gDNA from 33 nested PCR-negative animals identified seven qPCR positive cats with a median pVL of −0.7 log10 copies/cell (201,363 copies/10 6 cells). Analysis of cats classified as potentially transmissible and non-transmissible found no statistical difference between FFV pVLs. Of 27 FeLV-positive cats diagnosed by serological and/or molecular assays, 26 with available PBMC gDNA were FeLV qPCR-positive with a median pVL of 2.11 log10 copies/cell (1.29 × 10 8 copies/10 6 cells) ( Figure 1B) . Testing of 35 buccal swab gDNA samples identified four qPCR-positive cats with a median FeLV pVL of −0.55 log10 copies/cell (2.91 × 10 5 copies/10 6 cells).
cord-263200-ntq1f4ix	2016	
cord-263315-g7os15m1	2018	title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. In human and mouse plasmacytoid dendritic cells (pDCs), which are professional interferon-producing cells specialized in recognizing viral RNA and DNA through the endosomal Toll-like receptors (TLRs) TLR7 and TLR9, respectively, PLSCR1 was described as a TLR9-binding protein that plays a significant role in type-1 interferon responses in pDCs by regulating TLR9 expression and trafficking [57] . Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts. Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts.
cord-263699-gosqpg3k	2020	
cord-264526-bxpzo2xu	2020	
cord-265679-7gzont7l	2018	In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. Vero cells cultured in 24-well plates were washed with PBS for 3 times and inoculated respectively with single medium, or single PEDV, or PEDV pre-incubated with different concentrations of Caerin1.1. PEDV suspensions containing different concentrations of Caerin1.1 were pre-incubated for 1 h at 37 • C, and were serially diluted before they were inoculated on the 80% confluent Vero cell monolayers grown in the 96-well plates, followed by washing 3 times with PBS. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1.
cord-266901-oyevbxtc	2017	
cord-267012-45tre8rn	2018	While recombinant baculoviral vector expressing both VSV-G and influenza HA was shown to evoke both humoral and cellular immune responses and provided effective protection against lethal virus challenge in mouse and chicken hosts [26] , the high cytotoxicity of VSV-G protein [98] and its immediate inactivation by serum complement systems impedes the use of the element in a vaccine delivery vehicle [99] . The vaccine showed successful HA expression on its envelope, and mice vaccination studies showed that both the live and adjuvanted with inactive form of recombinant baculovirus induced HA-specific antibody responses and offered complete protection against lethal viral infection [101] . Moreover, recombinant baculovirus with CMV-polyhedrin dual promoter for expressing chimeric HA of H9N2 was shown to efficiently express HA in both mammalian and insect cells, induce strong immune response, and provide 100% protection against lethal H9N2 viral challenge in mice, unlike other vaccine candidates observed [34] .
cord-267709-i2loz1xb	2019	title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Finally, our data demonstrates that the antiviral effects of IFITM1 on cellular proliferation and HBV replication are partially restored when HBc is co-expressed with BAF200 in HBV-infected cells. First, BAF200C was co-transfected with either empty vectors or HBc into 293T cells, then the whole cell lysate was immunoprecipitated by an anti-Flag antibody and then subjected to western blot by anti-HA antibodies to detect the interacting proteins. (d) HepG2 cells were co-transfected with the pGC-FU-Flag-BAF200 and pCMV-HA vectors or pCMV-HA-HBc, and co-IP assays were carried out with anti-HA antibody or IgG. We co-transfected HBc and BAF200 into HepG2 cells, treated the cells with 500 U/mL IFNα, and detected the expression of IFITM1 by western blot (Figure 2d ).
cord-267733-fuz8r3vj	2016	This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein
cord-268788-jcu3pasy	2011	
cord-269249-7ubs3q6p	2019	
cord-270103-g9a72xf6	2018	Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. Some nucleoside analog drugs targeting specific viral polymerases (acyclovir for herpesviruses, zidovudine for human immunodeficiency virus (HIV), and sofosbuvir for hepatitis C virus (HCV)) have been successful in clinical trials [2] [3] [4] [5] and are currently in use for the treatment of virus-infected patients. However, in recent years, the antiviral activity of gemcitabine has also been reported against a broad range of RNA viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), HCV, poliovirus (PV), influenza A virus (IAV), HIV, and enteroviruses (EV) [13] [14] [15] [16] [17] [18] . Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion
cord-270380-1me7ugkg	2020	
cord-272010-kc0gi3cj	2020	The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. One potential therapeutic target receiving significant attention is the interaction between the SARS-CoV-2 spike (S) glycoprotein and its receptor, human angiotensin-converting enzyme 2 (ACE2). To better understand the interactions between membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins with their receptor, human ACE2, we sought to determine the cooperativity of ACE2 within the respective trimers. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2
cord-272018-txdc0c3j	2019	
cord-272391-0imlae98	2019	
cord-272459-w14finxf	2011	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.
cord-272666-3uidpr79	2018	
cord-273326-gmw8gl2r	2018	In this line, and contrary to above mentioned report [73] , CQ, an FDA-approved anti-inflammatory 4-aminoquinoline and an autophagy inhibitor widely used as an anti-malaria drug that is administered to pregnant women at risk of exposure to Plasmodium parasites, was shown to have anti-ZIKV activity in different cell types (Vero cells, human brain microvascular endothelial cells (hBMECs), and human neural stem cells (NSCs)), affecting early stages of the viral life cycle, possibly by raising the endosomal pH and inhibiting the fusion of the envelope protein to the endosomal membrane [74, 75] . Similarly, by using a drug repurposing screening of over 6000 molecules, it was found that emricasan, a pan-caspase inhibitor that restrains ZIKV-induced increases in caspase-3 activity and is currently in phase 2 clinical trials in chronic hepatitis C virus (HCV)-infected patients, protected human cortical neural progenitor cells (NPC) in both monolayer and three-dimensional organoid cultures, showing neuroprotective activity without suppression of viral replication [82] .
cord-273366-xd84f8ct	2020	Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways, whilst at the same time, IBV replication also results in the induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. Vero cells were infected with IBV and at the indicated time points, cells were fixed and labelled with anti-dsRNA to detect virus infection and with anti-G3BP1 to detect SG. Following identification of SG in IBV infected cells, the requirement for active virus replication in induction of granules was assessed. At 24 hpi, cells were fixed and labelled with anti-G3BP1 (red) to detect stress granules (SG) and IBV infected cells were detected with an anti-dsRNA antibody (green). Junin virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eIF2alpha phosphorylation
cord-273661-egpyvqrw	2013	
cord-273777-qb0vp9gr	2020	
cord-274569-jh0dyyz7	2015	
cord-277039-yo5ojr0s	2019	
cord-279691-v5kpmk0b	2012	
cord-280782-8gbktpt3	2019	
cord-281552-zfjy3m3i	2020	Here, we test E-derived peptides for membrane binding activity in vitro and confirm those identified as positive in the context of the full length protein expressed in two different cell types. Relative densitometry of the HSP and LSP bands revealed significant differences among the mutants with regard to their localisation to the different membrane fractions of E expressing insect cells ( Figure 5B ) and confirmed a role for the amphipathic MHV CoV E 50-64 peptide in membrane interaction. An amphipathic helix, EPTM, detected in the post-TM region of E, was suggested by bioinformatics analysis and assessed for direct membrane interaction in vitro by binding to GUVs. For comparison, the predicted E protein TM domain, ETM, and an established membrane active peptide from the influenza M2 protein were also included. Following expression of the complete E protein with mutations in the same identified peptide, altered membrane binding in two distinct cell types, mammalian and insect, was apparent.
cord-281837-knswbb2d	2012	An assay to measure the inhibition of virus-induced cell death in RD cells was first employed using 1 mg/mL of herbal extracts followed by EC 50 determination if the candidates possessed antiviral activity from the primary screening. DGFW but not DMSO protected the cells from virus-induced CPE (panel E versus F, Figure 2 ), indicating that DGFW inhibited viral replication. To test the mechanism of inhibition of viral entry into host cells by DGFW, we performed attachment and penetration assays. Unbound DGFW was removed, the cells were then infected with EV71 for 1 h, and the progeny viruses in the cells and culture medium were harvested for plaque assay at 10 h p.i. Similarly, EV71 was pretreated with DGFW or DMSO for 30 min at 37 °C, and the infectivity of the treated virus was then determined by plaque assay (Figure 6 ). A neutralization assay (EC 50 ) was used to test the antiviral efficacy of extracts or compounds by measuring the inhibition of CPE induced by enterovirus on RD cells.
cord-283756-ycjzitlk	2014	Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. Bats are known to have varying degrees of contact with domestic animals and commercial food crops [20, 21] , in particular contact of Pteropus giganteus bats with date palm sap producing trees in Bangladesh is considered a risk factor for human NiV infection [22] . It can be seen that while recent human infections of both NiV and MARV appear to be limited in geographical range (the red areas in Figure 2 ), there are a number of countries where bats have been identified as having the virus, but no human infection has been reported.
cord-284216-4sl8xfur	2020	
cord-285935-5rsk6g7l	2019	Cyclic peptides (CP) that had been developed to abrogate interaction of p6Gag and TSG101 and inhibited viral release of HIV Virus like particles (VLPs) [76] were tested for their activity against HEV [77] . The compounds RBV and mycophenolic acid (MPA), both of which target enzymes involved in nucleotide synthesis, are either already used as treatment against HEV or have been reported for their potential to inhibit the virus. So far, the antiviral activity against HEV of only four drugs (Sofosbuvir, pegIFN-α, Ribavirin and silvestrol) was approved in experimental settings beyond in vitro cell culture systems. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus infection Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo
cord-286343-s8n1ldol	2020	We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations. However, it was clear that there was a large reduction of SARS-CoV-2 RNA concentration in sewage between 14th April and 12th May. Positive and negative results were independently confirmed using a second real-time PCR platform (Stratagene 3000P) in a different NIBSC laboratory. However, it was clear that there was a large reduction of SARS-CoV-2 RNA concentration in sewage between 14th April and 12th May. Positive and negative results were independently confirmed using a second real-time PCR platform (Stratagene 3000P) in a different NIBSC laboratory (data not shown).
cord-287647-0nyquokt	2019	The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. In contrast in Japan, although an outbreak of diarrhoea occurred among ECoV-infected draft horses at one racecourse [4] [5] [6] , there have been no similar outbreaks subsequently, and all rectal swabs collected from diarrheic Thoroughbred foals were negative. Furthermore, only 2.5% of the rectal swabs collected from healthy foals in the largest Thoroughbred horse breeding region in Japan were positive for ECoV [13] . This study provides the first report of ECoV circulating in Ireland, the third European country with a significant horse industry where the virus has been detected in horses with enteric disease. This is the first report of ECoV detection in faeces samples from both foals and adult horses in Ireland. Low prevalence of equine coronavirus in foals in the largest Thoroughbred horse breeding region of Japan
cord-288058-oilurica	2020	To determine the effect of APN on coronavirus replication, the enterocytes were precultured with 1µg/mL hydrocortisone, 50 µM spermidine, 1 µg/mL insulin, 0.1 µM Wnt agonist, or 1% intestinal contents for 24 h prior to inoculation with PEDV CV777 Vero adapted strain, CV777 fecal suspension, and TGEV Miller. To determine the effect of APN on coronavirus replication, the enterocytes were precultured with 1µg/mL hydrocortisone, 50 µM spermidine, 1 µg/mL insulin, 0.1 µM Wnt agonist, or 1% intestinal contents for 24 h prior to inoculation with PEDV CV777 Vero adapted strain, CV777 fecal suspension, and TGEV Miller. The results show that pretreatment of primary enterocytes with hydrocortisone, spermidine, porcine insulin, Wnt agonist, and intestinal contents could stimulate the expression of APN and enhance the infection of PEDV CV777 Vero adapted and non-adapted strains and the TGEV Miller in the enterocytes.
cord-288556-o8i6j3b2	2020	We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and identified three different feline bocaviruses shed by 9/17 cats. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. Here, we analyzed a multi-facility outbreak of vomiting and diarrhea in cats using the following approaches: a commercial feline diarrhea panel of PCR tests for known enteric pathogens; viral metagenomics; and follow-up PCRs. Multiple mammalian viruses of varied origins were detected. DNA was extracted from each individual fecal sample (and one pool of 3, cat#973-975) shown in Table 3 plus 4 vomit samples using the QIAamp MinElute Virus Spin Kit (Qiagen, Hilden, Germany), and PCR assays were used for the detection of different viral nucleic acids in each sample.
cord-289273-zpyz1krq	2010	Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Recently, cellular BTB domain-containing proteins have been shown to function as substrate-specific adaptors of cullin-3 based ubiquitin ligase to target proteins for ubiquitination [54] [55] [56] [57] . Although the poxviral ankyrin repeat proteins contain no obvious structural domains at their C-termini, many of the proteins display a conserved sequence, which upon closer inspection was shown to resemble the F-box domain that functions in the recruitment of substrates to the cellular SCF (Skp-1, cullin, F-box) ubiquitin ligase complex [82] [83] [84] . The complex consists of cullin-1, which serves as the molecular scaffold, Roc1, a RING finger ubiquitin ligase, Skp1, the linker protein, and one of over 70 known cellular F-box proteins which function in substrate recruitment ( Figure 2D ) [84] [85] [86] .
cord-289757-jtvpfsiu	2011	Interestingly, when DNA isolated from peripheral blood mononuclear cells (PBMC) of these HTLV-I/II seroindeterminate individuals is amplified using polymerase chain reaction (PCR) assays, typically no HTLV-I or HTLV-II virus is detected (however, recent reports from Iran, Argentina, and Brazil have challenged this finding) [17] . Enhanced specificity of truncated transmembrane protein for serologic confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by western blot (immunoblot) assay containing recombinant envelope glycoproteins Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean Molecular analysis of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from Northeast Iran: Evidence of proviral tax, env, and gag sequences
cord-290127-51ljxy72	2020	While the S protein is by far the most studied region for vaccine designs, in silico analyses of potential immunogenic epitopes in the SARS-CoV-2 have suggested several domains within the N, M, and E protein as well as the non-structural proteins primarily focusing on T cell responses [21] [22] [23] [24] [25] . Looking at SARS, several vaccines using different viral vectors or DNA were able to induce high levels of neutralizing antibodies using the full-length S protein, which, in some models, provided protection against challenge [36] [37] [38] [39] [40] . When comparing different vaccine platforms, one study looked at the inactivated vaccines and adenovirus vectors expressing the S protein, or the N protein of SARS reported increased protection when utilizing the whole inactivated virus. A Phase I/II, randomized, placebo-controlled, observer-blind, dose-finding trial in the United States (NCT04368728/NCT04380701) is evaluating the safety, tolerability, immunogenicity, and efficacy of four SARS-CoV-2 RNA vaccine candidates (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) in healthy adults between 18 and 85 years old.
cord-292050-x3isowrt	2020	Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Screenings of experimentally verified SARS-CoV-2 interacting host proteins [7] have elucidated key infection mechanisms which, when compared to drug databases, have predicted a range of possible targets for repurposing. To assess whether the robust controllability classifications of the driver and virus interacting proteins are a result of the network''s connectivity structure, a randomization analysis was performed as developed in previous work [11] . The eight critical virus interacting proteins of the HIN become intermittent in the VIN, losing some control over infected network regulation. The eight critical virus interacting proteins of the HIN become intermittent in the VIN, losing some control over infected network regulation.
cord-292364-jhiimglg	2020	Comparative and phylogenetic analyses using sequence data of the three BIDVs and IDVs from Japan and other countries available in GenBank demonstrated that Japanese BIDVs, including the three BIDV isolates, were genetically distinct from other IDVs. Genotype classifications based on the rotavirus genotype classification revealed multiple genotypes of RNA segments 1–7. Our findings suggest that BIDVs of different genotypes and antigenicity are distributed and maintained in Hokkaido and provide new insights into molecular characteristics and the evolution of IDVs. Influenza viruses are enveloped, segmented, single-stranded, negative-sense RNA viruses, which belong to the family Orthomyxoviridae, and are currently classified into the following four species: influenza A, B, C, and D (IAV-IDV). Viral neutralizing antibody titers of serum samples collected in the acute (pre) and recovery (post) phases of BRD outbreaks that occurred at farms A and B against bovine influenza D viruses (HKD1 and HKD2) isolated from the two farms, as measured using a neutralization assay.
cord-292948-1n5ej08f	2020	title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs. Coronaviruses (CoVs) are an enveloped, single positive-strand RNA species of viruses belonging to the Coronaviridae family, which infect birds and mammals. Here, we document the epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) observed in general practice. To study the weekly number of HCoVs detected among ILI/ARI patients seen in general practice during the six influenza seasons, we gathered all samples collected by GPs for influenza surveillance and for the IRIIS study (Table 1 and Figure 1 ).
cord-294125-v2dr4hm0	2018	Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy. Binding to IFNARs leads to the activation of the Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT) signaling pathway and the formation of the interferon-stimulated gene factor 3 (ISGF3) complex, with the subsequent expression of IFN-stimulated genes [3] that establish an antiviral state and play important roles in determining the host innate and adaptive immune responses [4] . In the following sections, we discuss the antiviral mechanisms mediated by ISGylation of both viral and cellular proteins, with a focus on mitochondrial proteins, as we recently showed that ISG15 modulates essential mitochondrial metabolic processes such as respiration and mitophagy in macrophages, with important implications for innate immune responses [29] .
cord-294347-axkdf5vu	2016	Specifically, vectored vaccines can have advantages for (i) viruses for which a live attenuated vaccine might not be feasible (i.e., HIV); (ii) viruses that do not grow well in vitro (i.e., human papillomavirus, hepatitis C virus, and norovirus); (iii) highly pathogenic viruses that present safety challenges during vaccine development (i.e., SARS-CoV and Ebola virus); (iv) viruses that lose infectivity due to physical instability (i.e., respiratory syncytial virus (RSV)); and (v) viruses that can exchange genes with circulating viruses (i.e., coronaviruses, influenza viruses, and enteroviruses) [4] . Further, immunized mice by the intravenous route were completely protected against a lethal dose of influenza virus, suggesting that NDV can be a safe and effective vaccine vector for possible use in mammalian and avian species. Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus
cord-294842-aesiff1f	2014	Three-dimensional reconstructions of the WNV KUN replication sites revealed an intimate association of the rough ER (rER) with the bounding membrane of the VPs [20] (Figure 2B ), resembling the vesicles observed in DENV-infected cells. In cells infected with TBEV, one of the most important tick-transmitted viruses in Europe and Asia, virus particles and membrane-connected vesicles were also observed inside the ER [25] , similar to what was described for DENV and WNV KUN . Importantly, pulse-radiolabeling experiments localized sites of active RNA replication to the outer surface of single-membrane tubules [71] and isolation of the membranous replication factories and their subsequent visualization by EM revealed that they form rosette-like structures composed of virus-induced cytoplasmic vesicles [124] . Formation of plant RNA virus replication complexes on membranes: Role of an endoplasmic reticulum-targeted viral protein
cord-295044-eva0soja	2010	The disease pathogenesis has been conjectured and modeled largely from animal studies; initial models were using ectromelia infection of mice; some kinetic observations of virus shedding and viremia have been made in human studies of smallpox and monkeypox. challenged adult common squirrels (Sciurus vulgaris) with 10 6 pfu of MPXV Z-249 (Congo Basin clade) via IN, oral or scarification routes of infection [9] . A follow-up study found the LD 50 for the prairie dog MPXV model is approximately a hundred-times lower for the Congo Basin clade compared to the West African clade (5.9 × 10 3 and 1.29 × 10 5 , respectively) [15] , utilizing an IN route of infection. A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus Dosage comparison of Congo Basin and West African strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease
cord-295433-olmein3q	2019	Initial studies investigating animal sources of the virus from "wet markets" in the Guangdong province of China suggested that Himalayan palm civets and raccoon dogs were the most likely hosts responsible for human transmission [22] ; however, the role of bats as the original animal reservoir hosts of SARS-CoV was speculated as similar viruses were detected in them [27, 28] . A recent study found that 16 out of 30 camel workers surveyed in Saudi Arabia show evidence of prior MERS-CoV infection via seroconversion and/or virus-specific CD8+ T cell responses without any history of significant respiratory disease. The primary bat species being used to study the bat immune response to virus infections in vitro and in vivo are Pteropus alecto (black flying fox), Rousettus aegyptiacus (Egyptian rousette), and Artibeus jamaicensis (Jamaican fruit bat). Multiple studies with PEDV, SARS-and MERS-CoVs have identified accessory proteins that can effectively inhibit an IFN response in mammalian cells [12] [13] [14] [91] [92] [93] [94] [95] .
cord-295750-0gpyi4ii	2020	A partial open reading frame 7 sequence of the PRRSV2 isolate demonstrated a high identity with modified live vaccine-related strains from Denmark (93%) and wild-type VR2332 (92%). PRRSV, PCV2, swine influenza virus (SIV), porcine parvovirus virus (PPV), and porcine respiratory coronavirus (PRCV) in serum samples were detected using commercial polymerase chain reaction (PCR) kits (Vetbiochem, Russia) according to the manufacturer''s instructions. Phylogenetic analysis of a partial ORF7 sequence of the PRRSV2 strain isolated in the course of this study revealed that this strain was very dissimilar (88% identity) to the only known PRRSV2 strain (JXA1-related, sublineage 8.7) detected in East Siberia, Russia, in 2007. Comparison of Molecular and Biological Characteristics of a Modified Live Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine (Ingelvac PRRS MLV), the Parent Strain of the Vaccine (ATCC VR2332), ATCC VR2385, and Two Recent Field Isolates of PRRSV Genetic Analysis of ORF5 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Isolated in Vietnam
cord-296736-jsm6o5pq	2009	title: An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens The aim of this study was to modify real-time PCR assays to facilitate the rapid screening of respiratory samples for a comprehensive range of viral and bacterial pathogens. This tandem multiplex real-time PCR assay, in combination with the semi-nested picornavirus and human metapneumovirus PCR assays, tests for 35 respiratory agents from a sample volume of 180µL compared to 720 µL required for the individual assays. Further work is planned to incorporate the picornavirus and human metapneumovirus assays into the tandem multiplex real-time PCR assay, but so far we have been unable to design or use published real-time PCR primers and probes that detect all types of these viruses with the same sensitivity as our nested assays. A tandem multiplex real-time assay is presented which detects a comprehensive range of respiratory pathogens from a specimen sample of 180µL. Multiplex real-time PCR assay for detection of Influenza and human respiratory syncytial viruses
cord-296819-gztmidn2	2013	title: Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for ''Imported'' Viral Diseases (ENIVD). For the routine detection of WNV RNA using molecular techniques there are two distinct diagnostic settings: the first involves blood and organ donation screening from subjects living in an area where WNV circulation is known to be occurring, and the second involves the identification of viral genomes in serum, plasma and CSF samples from patients presenting with a clinical picture typical of WNV infection [21] .
cord-297092-oq14cwka	2020	This study developed whole genome sequencing methods to facilitate the control of SVA and provide a reference for the timely detection and prevention of other emerging infectious diseases. For the sequencing of cell culture samples, raw pass reads were mapped to the SVA reference genome (GenBank: MN164664) using Minimap2 [34] , then analyzed using Qualimap [35] , generating raw error rates and coverage information which was then visualized using GraphPad prism software (GraphPad Software, San Diego, CA, USA). After determining the consensus generation strategies for both sequencing methods, optimization was performed in terms of total input sequencing yield and the pre-treatment of raw reads using the cell culture virus in which the whole genome sequence was already known. In order to evaluate and compare the general performance of DRS and PCS for viral whole genome recovery, two whole genome sequencing runs using a cell culture-grown virus with a known reference sequence were carried out for each method (Table 1 ).
cord-297339-et2305rz	2012	In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of the classification. Based on our experience with other virus families, we conclude that the current sampling of filovirus genomic sequences needs to be considerably expanded in order to resolve these uncertainties in the framework of genetics-based classification. The DEmARC specifics include (i) the use of pairwise evolutionary distances (PEDs) instead of uncorrected p-distances, and (ii) a quantitative method to devise taxon levels and associated PED thresholds for virus clustering in a systematic and family-wide manner. The first selected threshold (PED of 0.120) results in seven clusters ( Figure 1B ) that match the official or tentative ICTV species of the family Filoviridae. In the high-sampling case of picornaviruses, no PED values with zero frequency are observed which suggests that the current sampling of filovirus genome sequences may strongly underestimate the natural genetic diversity in the family.
cord-297834-me1ajoyb	2014	The immune response is energetically expensive for wild animals, thus the findings of experimental studies will be critical for understanding the ecoimmunology of reservoir hosts of hantaviruses [6, 7] , and experiments using wild rodents in natural or semi-natural environments [8, 9] will be required to validate laboratory findings. Currently, three laboratory infection systems have been developed to study hantavirus infections of reservoir hosts: Seoul virus (SEOV) infection of the Norway rat (Rattus norvegicus), Puumala virus (PUUV) infection of the bank vole (Myodes glareolus), and Sin Nombre virus (SNV) infection of the deer mouse (Peromyscus maniculatus) [12, 14, 16] . Experimental data have also shown that patterns of the expression of genes related to the immune response are different in infected males and females [32] , and it is likely these differences have important roles in hantavirus ecology.
cord-300625-fvirvpyl	2020	In addition to the global structural genomics, an initiative that focuses on determining the 3D structures of individual proteins on a genome scale [34] , as well as to the specific efforts aimed at rapid structural characterization of proteins in emerging viruses [35] [36] [37] [38] , multiple works have used comparative modeling to predict the structures of protein-protein interaction complexes [39] [40] [41] , facilitate structure-based drug discovery [33, 42, 43] , infer protein functions [44] , determine the macromolecular interaction network [45] [46] [47] [48] , and provide molecular insights into the viral evolution [49] [50] [51] . To do so, we structurally characterized individual proteins as well as intra-viral and human-virus protein complexes, extracted the information on their interaction interfaces and ligand binding, and superposed the evolutionary difference and conservation information with the binding information.
cord-301633-t8s4s0wo	2020	Similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections, patients exhibited symptoms of viral pneumonia including fever, difficulty breathing, and bilateral lung infiltration in the most severe cases [1] . A range of disease has been observed highlighted by fever, dry cough, shortness of breath, and leukopenia; patients have included mild cases needing supportive care to severe cases requiring extracorporeal membrane oxygenation; however, compared to SARS-CoV (10% mortality) and MERS-CoV (35% mortality), the 2019-nCoV appears to be less virulent at this point with the exception of the elderly and those with underlying health conditions. In the early part of the outbreak, the absence of infection in health care workers argued for inefficient human to human spread and distinguished 2019-nCoV from both SARS-CoV and MERS-CoV.
cord-301810-vtgdqart	2019	Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). At 5 days following challenge with IBV GA98, vaccinated/challenged birds had significantly lower RNA loads compared to positive controls at all collection times and in all tissue samples, with the exception of cecal tonsil at 24 WOA (Table 1 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ).
cord-302716-wfla3l20	2019	Viruses can be differentiated by their specific morphology (ultrastructure): shape, size, intracellular location, or from the ultrastructural cytopathic effects and specific structures forming in the host cell Upolu, Aransas Bay [22] , Sinu [23] , and Trinity [24] orthobunyaviruses [25] [26] [27] , nyamiviruses [28] , a new reovirus from Cameroon (Fako virus) [29] and Colombia [30] , a new paramyxovirus [31] , an insect-specific (capable of replication in insects but not in vertebrates) alphavirus [32] , a new flavivirus genus [33] and other novel flaviviruses [34] [35] [36] [37] and rhabdoviruses [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] . Insect-specific viruses isolated recently from mosquitoes and phlebotomine sandflies have been characterized and proposed to represent a new genus (Negevirus) related to genera of mite-infecting plant viruses (Blunervirus, Cilevirus, and Higrevirus) in the new family Kitaviridae [49, 73] , or novel members of Entomobirnavirus, family Birnaviridae ( Figure 10D ).
cord-302953-gr2kk9w4	2020	In Phase 1, during the first 7 to 8 days post infection (DPI), both infectious virus and viral RNA increase rapidly, followed by clearance of infectious virus that occurs primarily through cooperative effects of anti-SINV antibody and the cytokine interferon-gamma (IFN-γ) [6] [7] [8] [9] . Gbp2 ( Figure 2A ) and Irgm ( Figure 2B ), two genes associated with autophagy [25] , were highly expressed by SINV-infected dAP-7 cells treated with IFN-γ, as were Oasl2 ( Figure 2C ), a member of the 2''-5''oligoadenylate/RNaseL system [26] , and Rsad2 ( Figure 2D ), which encodes viperin, a protein that interferes with assembly and release of many viruses [27] . To determine the effects of IFN-γ signaling on immune cell subsets after SINV infection, cells isolated from the CLNs and brains of WT, Ifng −/− and Ifngr1 −/− mice were examined by flow cytometry. To determine the effects of IFN-γ signaling on immune cell subsets after SINV infection, cells isolated from the CLNs and brains of WT, Ifng −/− and Ifngr1 −/− mice were examined by flow cytometry.
cord-305857-2409me0p	2014	In recent years, bats have been implicated in numerous emerging infectious disease events and have been recognized as important reservoir hosts for viruses that can cross the species barrier to infect humans and other domestic and wild mammals [3] . Persistent viral infections occurring among long-lived bats, coupled with their often gregarious roosting behavior, could greatly increase the potential for intra-and inter-species transmission of viruses [7] , especially in summer and winter periods. To study the variation in EBLV-1-antibody prevalence, we conducted two analyses: first, three explanatory variables (sex, species and year) were first screened using a univariate analysis and a chi-square test to check for statistically significant associations with serological status (0: negative; 1: positive). We report the results of the prevalence of specific EBLV-1 neutralizing antibody analysis from the 2004-2012 period in nine bat species roosting in the same refuge.
cord-306004-amv0los1	2019	Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. MERS-CoV infection in these animals merely causes mild upper respiratory tract infection [17, 18] , but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species [19] [20] [21] [22] . Given the fact that experimental in vivo infection studies and DPP4 expression analysis in different animal species revealed that dromedary camels are not the only animals in which MERS-CoV has an upper respiratory tract tropism [17, 18, 83, 84] , it is then relevant to question whether other animals can potentially spread MERS-CoV as well.
cord-307046-ko3bdvo0	2019	Complete genome sequences are now available for many of the archived isolates, allowing more accurate taxonomic assignments, analysis of their phylogenetic and evolutionary relationships with other viruses, and evaluation of the potential risks they may present to humans and wild or domestic animal populations. Scientists in these field laboratories were involved in the detection and investigation of human diseases in their respective geographic regions, surveying human and animal populations for serologic evidence of past viral infection, and searching for viruses in a wide variety of arthropods, mammals, birds, reptiles, and amphibians [2] . The family contains several serious human pathogens, including dengue, yellow fever, Zika, Japanese encephalitis, West Nile, and tick-borne encephalitis viruses (all arboviruses in the genus Flavivirus) and the hepatitis C virus (a member of the genus Hepacivirus).
cord-307110-eiobmxp2	2019	In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Synthetic sequences of 12 coronavirus spike S1 subunits (HCoV-HKU1 (GB: YP_173238.1), MERS-CoV (GB:YP_009047204.1), SARS-CoV (GB: AAX16192.1), HCoV-OC43 (GB: AAR01015.1), HCoV-229E (GB: NP_073551.1), HCoV-NL63 (GB: YP_003767.1), TGEV (GB: ABG89325.1), PEDV (GB: AOG30832.1), BCoV (GB: P15777.1), PDCoV (GB: AML40825.1), FCoV type 1 (GB: FJ938060.1), FCoV type 2 (GB: AY994055.1)) and different domains of PEDV S1 subunit (S1 0 and S1 A-D , as identified and described in [40] ) were cloned into pCAGGS expression plasmids as described previously [41] .
cord-308201-lavcsqov	2019	Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Even though no clear cause and effect link has ever been made with the onset of human neurological diseases, their neuropathogenicity is being increasingly recognized in humans, as several recent reports associated cases of encephalitis [244] , acute flaccid paralysis [271] and other neurological symptoms, including possible complications of HCoV infection such as Guillain-Barré syndrome or ADEM [249, [272] [273] [274] [275] [276] [277] [278] [279] . Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short-and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells.
cord-309239-6lso1w0o	2016	The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen first described from Saudi Arabia in 2012 [1] that can cause severe respiratory disease and death in roughly 36% of infected humans [2] . There is considerable field and experimental evidence that dromedary camels serve as an important reservoir host involved in transmission to humans [3] [4] [5] [6] [7] [8] , but whether other livestock such as goats, sheep, and horses play a role in transmission has only been assessed indirectly. The objective of this study was to determine if goats, sheep, and horses can be infected with MERS-CoV and assess their potential importance in viral transmission. Sheep, goat kids and horses were each inoculated intranasally with 1.4 × 10 6 to 1.9 × 10 6 plaque-forming units (PFU) of a low passage human isolate of MERS-CoV (strain HCoV-EMC/2012) propagated in Vero E6 cells as described previously [11] .
cord-309378-sfr1x0ob	2020	COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed. Moreover, closing schools postpones the peak of the epidemic (by about one month in case of the above setting), suggesting that children may play a significant role in transmission due to their large number of contacts, even though they give negligible contribution to the overall mortality, cf. As control measures are being successively relaxed since May 4, we established an age-structured compartmental model to investigate several post-lockdown scenarios, and projected the epidemic curves and the demand for critical care beds assuming various levels of sustained reduction in transmission.
cord-309571-a0xu1d56	2020	With intensive care units operating at maximum capacity and such staggering mortality rates reported, it is imperative during this time-sensitive COVID-19 outbreak to identify patients with an increased risk of adverse outcomes and/or myocardial injury. found that myocardial injury, defined by raised serum cardiac troponin I (cTnI) levels, in COVID-19 patients was associated with over 50% mortality rate [12] . In the study by Wang et al., 36 out of 138 (26.1%) COVID-19 patients were admitted to the ICU with severe symptoms, all of whom had significantly elevated serum cTnI and CK-MB levels (p = 0.004 and p < 0.001, respectively) compared to non-ICU patients [11] . cTnI provides remarkable prognostic value for patients at increased risk of worsening outcomes and in-hospital mortality, though studies have also shown the association of raised CK-MB and BNP levels with more severe symptoms of COVID-19.
cord-309623-2ngr682l	2017	Previous studies have reported that infectious bronchitis virus (IBV) infection can produce cytopathic effects (CPE) and apoptosis in some mammalian cells and primary cells. The Beaudette strains were used previously to study the resistance of IBV to the antiviral state induced by type I interferon (IFN) [7] , induction of apoptosis through endoplasmic reticulum stress in Vero cells by IBV infection [8] and activate autophagy by IBV nonstructural protein (NSP) 6 [9] . The rate of apoptosis significantly increased at 12 h.p.i. in virus-infected cells when compared with the mockInfection of HD11 cells with IBV Beaudette caused cell death in a time-and dose-dependent manner, as tested by CCK-8 assay. The results also showed that activation of caspase-9 in IBV Beaudette-infected cells was regulated by decreased expression of Bcl-2 and increased expression of Bax. The caspase-3 activation and virus-induced apoptosis might be triggered through both extrinsic and intrinsic pathways.
cord-309635-1tgovkr7	2020	Hemagglutinin (HA) glycoprotein is an important focus of influenza research due to its role in antigenic drift and shift, as well as its receptor binding and membrane fusion functions, which are indispensable for viral entry. Similarly, RBS of influenza B HA is composed of the 140-loop, 190-helix, and 240-loop, which are structurally equivalent to the 130-loop, 150-loop, and 190-helix Receptor specificity can also continue to evolve when seasonal viruses circulate in the human population, due to natural mutations that are likely a response to immune selection pressure. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin Design of nanoparticulate group 2 influenza virus hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages
cord-309693-f2htekhz	2017	To develop an effective bivalent oral vaccine against TGEV and PEDV infection, the D antigenic site of the TGEV spike (S) protein and the major antigen site (core neutralizing epitope—COE) of the PEDV S protein were used as immunogens, and the enhanced green fluorescent protein (eGFP) gene was used as a reporter to construct genetically engineered Lactobacillus casei rLpPG(F)-T7g10-eGFP-6D-COE. The results showed that levels of anti-PEDV and anti-TGEV serum immunoglobulin G (IgG) and mucosal secreted immunoglobulin A (sIgA) antibodies obtained from the mice immunized with rLpPG(F)-T7g10-eGFP-6D-COE, as well as the proliferation levels of lymphocytes, were significantly higher than those in mice orally administered phosphate-buffered saline (PBS) or rLpPG-T7g10. This was evidenced by significantly higher levels of virus-neutralizing antibodies, anti-PEDV/TGEV serum IgG, and mucosal sIgA in mice orally immunized with rLpPG F -T7g10-eGFP-6D-COE, compared to the levels for the rLpPG-T7g10 or PBS groups.
cord-310255-aixq5mhf	2020	More recent evidence highlights how viruses can regulate and/or depend on the ion channels expressed by host cells, highlighting them as new host targets for therapeutic intervention (reviewed by Hover et al., 2017) [14] . We then discuss how intracellular ion channels contribute to the Two-pore channels 1 and 2 (TPC1/2) Gunaratne et al., 2018 [34] Severe fever with thrombocytopenia syndrome virus (SFTSV) Unknown channel Li et al., 2019 [35] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Two-pore channel 2 (TPC2) Ou et al., 2020 [36] Bunyamwera orthobunyavirus (BUNV) Two-pore domain K + (K 2P ) Hover et al., 2016/18 [28, 37] Hazara orthonairovirus (HAZV) Unknown K + channel Punch et al., 2017 [38] Charlton et al., 2019 [39] Human immunodeficiency virus (HIV) G-Protein coupled inwardly rectifying K + (GIRK) ATP-sensitive K + K ATP Dubey et al., 2019 [40] Merkel cell polyomavirus (MCPyV) 
cord-310579-tnxokfwu	2020	title: Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene In the phylogenetic trees inferred from the D1-D2 datasets of the S gene ( Figure 2 , Supplementary Figures S1 and S2) , the PEDV strains were classified into five sub-genogroups (G1a, G1b, G2a, G2b, and G2c), which were previously designated [8] . In the phylogenetic trees inferred from the D1-D2 datasets of the S gene ( Figure 2 , Supplementary Figures S1 and S2) , the PEDV strains were classified into five sub-genogroups (G1a, G1b, G2a, G2b, and G2c), which were previously designated [8] . Supported by high posterior probability values (0.90-1), the phylogenetic trees inferred from the D3-D4 datasets of the N gene (Figure 3, Supplementary Figures S3 and S4) suggested that the classification of PEDV strains into four S gene-based sub-genogroups G1a, G1b, G2b, G2a/G2c was more reliable. Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China
cord-310734-6v7oru2l	2020	By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. Overall, a large number of phage-related sequences were detected (77.3% of viral read pairs and 39.9% of viral contigs), likely representing the most abundant entities infecting bacteria present in the bat digestive system, which exhibited similarity mostly to the families Inoviridae, Siphoviridae, and Myoviridae ( Table 1 ). Several mammalian viral families, supported by the contigs and sequencing reads, have been identified previously in New World [23, 24, 26] and Old World [17, 18, 89] bat species. Table S4 : Read pairs and contigs classified as similar to viruses and not taxonomical assigned to viral families identified in anal and oral swab samples of Tadarida brasiliensis obtained by metagenomics using Illumina technology.
cord-311008-b7xjlqg3	2019	Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. The remarkable diversity of plasma membrane proteins implicated in filovirus cell entry prompted us to analyze twelve cell lines for a potential correlation of host factor expression to filovirus susceptibility. We could show that the neuroblastoma SH-SY5Y cell line is specifically resistant to filovirus infection although all intracellular proteins known to be essential were expressed, and although its overall transcriptome was very similar to that of susceptible cell lines. Heterokaryon assays revealed that SH-SY5Y cells did not express a dominant restriction factor that inhibited filovirus GP-driven cell entry, but recombinant GP could not bind to their plasma membrane. In SH-SY5Y cells, however, an ectopic expression of any potential attachment-promoting plasma membrane protein of filoviruses, such as DC-SIGN, Axl, Mer, or TIM-1, conferred susceptibility to filovirus GP-driven transduction or infection.
cord-311205-3uwiys4a	2015	In addition, amino acid residues of the central region of some NS4A peptides might bind directly to the liposome leading to the disappearance of the corresponding NMR signals. In addition, amino acid residues of the central region of some NS4A peptides might bind directly to the liposome leading to the disappearance of the corresponding NMR signals. Finally, amino acid residues in the C-terminal region of NS4A(1-48) from T33 to L48 show the smallest reduction in the free state peak intensities upon liposome addition (Figure 2A) . Inspection of HSQC spectra of mutant NS4A(1-48, L6E;M10E) in buffer and with increasing amounts of sonicated POPC liposomes revealed no changes in cross peak positions and only a minor Finally, amino acid residues in the C-terminal region of NS4A(1-48) from T33 to L48 show the smallest reduction in the free state peak intensities upon liposome addition (Figure 2A) .
cord-312001-8p7scli8	2019	Consequently, animal cells have evolved devoted pathways which (1) sense and recognize pathogen-associated molecular patterns (PAMPs) and, more particularly, virus-associated molecular signatures; (2) initiate signaling cascades stemming from the site of detection, translocating the information to the nucleus; and (3) induce a transcriptional program that confers an antiviral state to the host ( Figure 1 ). While the cytosolic recognition of viral RNA is almost exclusively mediated by RLRs, several proteins have been proposed to play a role in DNA sensing and triggering innate immune responses, such as the DNA-dependent activator of IFN-regulatory factors (DAI), DDX41, RNA polymerase III, IFI16 and DNA-PK [62] [63] [64] [65] [66] [67] . Although the pathway leading to the transcriptional activation of Vago is still poorly understood in insects, these studies established that DExD/H-box helicase containing proteins, like Dicer and RLRs, may represent an evolutionarily conserved set of viral nucleic acid sensors that direct antiviral responses in animals [159] .
cord-312272-g4n426cm	2019	title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells To determine whether these results were caused by the emergence of viruses containing mutations, the intracellular RNA was isolated after infection with P7, P10, P15, and P19 EAVGp3-HA virus and subjected to RT-PCR, followed by sequence analysis ( Figure 2C ). To determine whether these results were caused by the emergence of viruses containing mutations, the intracellular RNA was isolated after infection with P7, P10, P15, and P19 EAVGp3-HA virus and subjected to RT-PCR, followed by sequence analysis ( Figure 2C ). We studied the co-localization of the Gp3-HA, E protein, and N protein in EAV-infected BHK-21 cells using immunofluorescence microscopy (18 h p.i.). The tagged Gp3 in the virus context might facilitate research on the biology of EAV, e.g., in this study, we analyzed the localization of the Gp3-HA in the infected cells.
cord-313161-07iwwsfz	2014	Furthermore, sequential immunization with SIN and VEE replicon particles expressing the type 1 HIV gp140 envelope (Env) and trimeric Env protein in MF59 adjuvant provided partial protection in macaques against intravenous challenges with high doses of simian-human immunodeficiency virus (SHIV) [61] . In another study, chimeric VEE/SIN replicon particles were applied for the expression of measles virus hemagglutinin (H) and fusion (F) proteins, which elicited high-titer neutralizing antibody and IFNɤ-producing T-cells in macaques after intradermal vaccination [48] . Furthermore, vaccination with recombinant particles expressing the P1A gene [105] and the human papilloma virus (HPV) E7 gene [89] from SFV and VEE vectors, respectively, provided protection against further tumor development in mice. When TRAMP mice were prophylactically immunized with a prostate stem cell antigen (PSCA) DNA plasmid followed by VEE-PSCA particle administration, a specific immune response and anti-tumor protection were observed in 90% of vaccinated animals [102] .
cord-313312-h607itv2	2020	Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. The clinical trial finding that subjects with a limited range of cross-reactive antibodies from a prior Japanese Encephalitis vaccine were able to enhance yellow fever vaccination, by prolonging vaccine viremia duration that leads to higher antibody titers, thus hints at the possibility that whether pre-existing antibodies inhibit or augment flavivirus infection will depend on both antibody titers and the type/specificity of antibodies produced [85] . By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity. By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity.
cord-313439-cadyykks	2019	Studies evaluating sensitivity and specificity of the detection of serum antibodies in comparison to either histopathology, a combination of diagnostic tests or clinical suspicion of feline infectious peritonitis (FIP). Recent studies evaluated the use of a quantitative RT-PCR (RT-qPCR) to detect FCoV RNA in FNA samples of the mesenteric lymph nodes and other abnormal tissues of clinical cases [119, 140] and hypothesized that this technique would be a useful tool to diagnose FIP for veterinary practitioners, especially in cats without effusion. Sensitivity and specificity from different studies evaluating the detection of feline coronavirus (FCoV) spike (S) gene mutations in tissue samples. RT-nPCR and subsequent S gene sequencing of serum and plasma samples from cats with FIP (diagnosed by histopathology ± IHC or by positive immunofluorescence in effusion) and control cats (diagnosed with another disease either ante or post mortem) revealed a sensitivity of only 7%, which confirms the very low virus load in blood.
cord-314340-ltx4w9zh	2018	During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). Indeed, 5 µM of AA treatment could inhibit histone H3 acetylation as demonstrated by the reduced levels of H3K9ac relative to the control, but AA increased the levels of H3K9ac in the context of virus infection in comparison to the mock treated but infected cells ( Figure 3E ,F).
cord-314505-7qh8dsew	2019	The induction of the IFN response following viral infections fundamentally changes the bone marrow microenvironment ( Figure 1B) , leading to the enhanced differentiation of myeloid cells [24] and emigration of neutrophils and monocytes to the site of infection, which is facilitated by chemokine gradients interacting with their cognate receptors ( Figure 1A ) [25] . TLR stimulation after phagocytosis activates the NF-κB signaling cascade, resulting in the release of inflammatory cytokines such as TNF-α, IL-1, and IL-6 from monocytes [4] to control virus infections by direct antiviral mechanisms and the recruitment of other leukocytes. Taken together, these findings suggest that type I IFN signaling drives a balance of pro-and anti-inflammatory effects on the functions of monocytes and neutrophils in response to viral infections; providing protective immunity while simultaneously limiting immunopathology. Importantly, viruses and virus-mediated tissue damage stimulate both neutrophils and monocytes, triggering a cascade of cytokine/chemokine-mediated innate immune responses.
cord-314891-brgtwxhe	2018	Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC(50) values in the low micromolar range (0.6 μM and 2.5 μM, respectively). The combined inhibitory effects of nitazoxanide (0 to 0.6 µM) and 2CMC (0 to 4 µM) were tested over a range of combinations against FCV in the cell culture using the plaque reduction assay. Of the six NNI compounds tested in the current study, PPNDS and quercetagetin showed an inhibition of FCV RdRp activity with IC 50 values in the low micromolar range (Figure 2 and Table 1 ). Finally, we reported the identification of two compounds (nitazoxanide and 2CMC) with antiviral activity against FCV in cell culture at low micromolar concentrations with a potential combinational therapeutic utility to treat FCV-infected cats.
cord-315164-nidgnvvi	2020	Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. In the present study, we sought to investigate the presence and molecular diversity of AdVs in wild African NHPs, including great apes (gorillas and chimpanzees), macaques and other monkeys (baboons, green monkeys), living in close proximity to or outside human settlements.
cord-317026-9zgc6xrb	2019	In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method utilizing ECoV spike S1 protein was developed in two formats, and further validated by analyzing 27 paired serum samples (acute and convalescent sera) from horses involved in an ECoV outbreak and 1084 sera of horses with unknown ECoV exposure. On the other hand, serological assays can be used to support the diagnosis of a clinical ECoV infection by showing seroconversion or a significant increase in antibody titer in paired serum samples. For the six horses that did not show a significant rise in VNT, five serum samples collected at the acute stage already had high antibody levels as shown by ELISA and neutralization assay (mean OD value > 2.6, mean VNT > 9, Table S1 ). For the six horses that did not show a significant rise in VNT, five serum samples collected at the acute stage already had high antibody levels as shown by ELISA and neutralization assay (mean OD value > 2.6, mean VNT > 9, Table S1 ).
cord-317037-1qydcc5e	2020	Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. HIV-infected U1 macrophages upon Cigarette smoke condensate (CSC) treatment enhanced the packaging of IL-6 in EVs; IL-8 served as a biomarker for HIV patients with altered immune function due to alcohol and tobacco abuse [20, 116, 117] Host protein APOBEC3G Inhibit replication of viral infectivity factor (vif) -deficient and wild-type HIV-1 in recipient cells [118] miRNA vmiR-88 and vmiR-99 Hepatocytes secreted exosomes participate in virus replication [142] Viral miRNAs HBV-miR-3 Represses viral protein production and HBV replication [143] HTLV-1 Viral proteins gp61, Tax, and HBZ Increase cell-to-cell contact and promote a potential increase in viral spread [144] Zika Viral genetic material and protein RNA and ZIKV-E EVs derived from Infected C6/36 cells promote infection and activation of monocytes with enhanced TNF-α mRNA expression.
cord-317496-6o2upns3	2019	In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). Interestingly, Viruses 2019, 11, 682 9 of 18 when viral RNA was isolated from feces of 21-day-old piglets at seven days post-vaccination (see below) and rTGEV-RS-SPEDV virus was sequenced, the same modifications were observed. An attenuated chimeric rTGEV virus expressing the ectodomain of a virulent US PEDV S protein (rTGEV-RS-SPEDV) was engineered as vaccine candidate for PEDV and evaluated in a young piglet model system. An attenuated chimeric rTGEV virus expressing the ectodomain of a virulent US PEDV S protein (rTGEV-RS-SPEDV) was engineered as vaccine candidate for PEDV and evaluated in a young piglet model system.
cord-317587-rrx2r4n2	2019	title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs. Infectious bronchitis (IB) is one of the major viral diseases affecting the poultry industry globally. Our results indicated that there was a remarkable change in genetic diversity, dominant genotypes, and selection pressure of IBV strains in southern China over the past decade compared with the previous period of 1985-2007. Molecular characterization of major structural protein genes of avian coronavirus infectious bronchitis virus isolates in southern China
cord-317715-xtsi663k	2012	Reporter gene activation (FFL) is shown as percentage (%) of LCMV NP-NP wt interaction (pC-NP-VP16 and pC-NP-GAL4) after normalization of transfection efficiencies with the Renilla luciferase expression plasmid pRL SV40 (ii). Unexpectedly, the D471A substitution impeded both NP-NP and NP-Z interactions, as well as NP functions in replication and transcription of the LCMV MG and the ability of NP to counteract SeV-mediated induction of the host IFN-I response, suggesting that change D to A at position 471 might have affected the overall structure of NP without affecting its stability as reflected by its unchanged expression levels determined by WB using anti-VP16 ( Figures 6A and 6B ) or anti-HA ( Figures 6C and 6D) antibodies. (C) Replication and transcription activity: BHK-21 cells were co-transfected with the LCMV MG as described in Figure 3 together with expression plasmids for the viral polymerase (L) and wt or indicated mutant NPs, and pSV40-Cluc expression vector to normalize transfection efficiencies.
cord-320015-lbr2q4qh	2011	Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions.
cord-320212-fw51w4nm	2012	When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. In all analysis programs, the nucleotide or amino acid sequences were aligned to other strains and were therefore approximate positions on the replicase gene. Breakpoint nucleotides for strains DL52 and DL54 (when aligned to genogroup I strains) occurred between nt 84-592 and 84-401, respectively ( Figure 5 a, b) , corresponding to the approximate amino acid breakpoint positions of 133-197 within the replicase gene. Human Noroviruses, a positive sense ssRNA virus with a genome length of 7400-8300 nt, are considered to belong to a prototype strain if they share approximately 85% overall nucleotide sequence identity and a high amino acid sequence identity (>95%) in the polymerase gene [20] .
cord-320921-eumuid3r	2019	Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Besides dromedary camels, other animal species, i.e. llamas, alpacas, and pigs have been shown to be susceptible and develop upper respiratory tract infection upon experimental intranasal MERS-CoV inoculation [9] [10] [11] . We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ).
cord-321013-8pkrg0mx	2014	The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. The M protein is the main core shell component and a 16 amino acid domain (aa 237-252) on the CTD of M protein binds directly to N protein via an ionic interaction, leading to specific genome encapsidation in the budding viral particle [81] [82] [83] .The N protein therefore plays an essential structural role in the CoV virion through a network of interactions with (i) the genomic RNA; (ii) M protein and (iii) other N proteins. Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA
cord-321080-pgxxkfc0	2019	We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. As shown in Figure 2 and Table 1 , combining HR2P-M2 and m336 resulted in strong synergistic inhibitory activity against MERS-CoV pseudovirus infection with CI values of 0.13-0.20 for 50-90% inhibition, including potency enhancement of 12.9-to 18.9-fold for m336 and 8.4-to 12.9-fold for HR2P-M2.
cord-321441-t1v0pu0w	2020	New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5''-terminal extensions driving the evolution of the orthoreovirus'' polycistronic genome segments and their encoded FAST and fiber proteins. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. MdRVs are divided into two subgroups, the "classical" and "novel" MdRVs. Classical Muscovy duck reoviruses (MdRVc) possess a bicistronic S4 genome segment encoding a truncated fiber protein of 269 residues and a p11 protein that lacks sequence similarity to the p10 FAST proteins of ARV, ARVN, and NBV ( Figure 1B ) [50] .
cord-321673-v5o49ees	2015	Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Noticeably, these proteins oligomerize in cell membranes to form ion conductive pores, which generally display mild ion selectivity, indicating that viroporins do not show preference for particular ionic species. Influenza viruses lacking M2 ion conductivity, presented either a 15-fold reduction of viral titer in tissue culture [74] , or showed a standard production in cell culture but a restricted growth in the nasal turbinates of infected mice [75] . Several compounds inhibit viroporin ion conductivity in artificial lipid membranes, and some of them efficiently reduce viral growth when administered to infected cells. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells
cord-322206-roxa3ix6	2020	Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5′-UTR and 3′-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification. Here, we applied RNA-based metatranscriptomics associated with Ion Torrent deep sequencing and a newly developed Bioinformatics approach to the high-quality reconstitution of viral genomes.
cord-323569-ksodnkic	2019	title: A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. Immunization of mice with ISA 201VG mixed with Poly (I:C)-adjuvanted SBLP resulted in significant increases in SUDV GP-specific IgG, IgG1, and IgG2a and SUDV pseudotyped virus-neutralizing antibody titers, which are considered to be important correlates of protection [34, 49] . Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice
cord-323585-iv2dcpqj	2015	The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. The GST or GST-NS5A fusion proteins expressed in Escherichia coli BL21(DE3) were purified with glutathione Sepharose 4B resin and incubated with the lysate of HEK293T cells overexpressing the Myc-tagged eEF1A. The immunoprecipitate was analyzed by Western blotting using the anti-Flag MAb (1:1000) and a rabbit anti-Myc PAb (1:500); (D) Co-IP analysis of eEF1A and NS5A by the anti-Myc MAb. HEK293T cells were cotransfected with the indicated plasmids (+) or empty vectors (''), the cell lysate was collected at 48 h post-transfection (hpt), incubated with the anti-Myc MAb and Protein G-Agarose. The bound proteins were analyzed by immunoblotting using the anti-Myc monoclonal antibody (MAb) (1:1000); (B) eEF1A interacts with the CSFV IRES in a dose-dependent manner. The bound proteins were analyzed by immunoblotting using the anti-Myc monoclonal antibody (MAb) (1:1000); (B) eEF1A interacts with the CSFV IRES in a dose-dependent manner.
cord-323995-cpn34j02	2017	To test this hypothesis, we analyzed the kinetics of CypA RNA expression by quantitative real-time PCR, intracellular CypA (inCypA), and secreted CypA (sCypA) protein levels by Western blot analysis following HCMV infection of HFF cells. To test this hypothesis, we analyzed the kinetics of CypA RNA expression by quantitative real-time PCR, intracellular CypA (inCypA), and secreted CypA (sCypA) protein levels by Western blot analysis following HCMV infection of HFF cells. Moreover, we found that endogenous CD147 was targeted by HCMV-encoded miR-US25-1-5p at the 3 UTR, which could replace CD147-specific siRNA mimics in inhibiting the CD147-mediated early innate immune response to HCMV infection ( Figure 4) . Moreover, we found that endogenous CD147 was targeted by HCMV-encoded miR-US25-1-5p at the 3 UTR, which could replace CD147-specific siRNA mimics in inhibiting the CD147-mediated early innate immune response to HCMV infection ( Figure 4) .
cord-324617-yok7mh70	2020	Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. The addition of LT1 to the vaccines significantly enhanced the DENV2-specific serum IgG responses elicited in the mice immunized via the TC or ID route, with the maximal values reached two weeks after the third vaccine dose ( Figure 1A ,B). The ID-immunized mice showed significant differences in DENV2-specific serum IgG responses in the presence of LT1, particularly in the group immunized with 50 µg of the tested antigen ( Figure 1D ). The ID-immunized mice showed significant differences in DENV2-specific serum IgG responses in the presence of LT1, particularly in the group immunized with 50 µg of the tested antigen ( Figure 1D ).
cord-325574-4zf9qtlh	2018	MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans. By reviewing changes involving humans and camels over the past 30 years in Qatar, this study sought to identify the key drivers of the emergence and spread of MERS-CoV. The main themes that were covered during the interviews included: (changes in) people''s living conditions; customs and purposes of camel ownership; cultural habits related to camels; educational level and personal behaviors of camel owners and workers; camel movement; demographic distribution of camels in Qatar; camel farming practices: feeding, grazing, and slaughter.
cord-325823-bt7xo9iq	2020	In January 2019, a 35-year-old man, a wood merchant from Kissidougou, Forest Guinea, presented himself at several health centers with persistent fever, frequent vomiting and joint pain. Due to the similarity of symptoms with malaria, Lassa fever is still a disease that is difficult to recognize and that may remain undiagnosed in health centers in Guinea. However, Guinea has very few reported acute human cases, and only a few studies have a posteriori described acute Lassa fever cases in the prefectures of Kindia, Faranah, Kissidougou, Guekedou, Macenta and N''Zérékoré in 1992 and 1996-1999 [12] [13] [14] . A total of 41 individuals in contact with the case in Kissidougou (n = 7), Mamou (n = 32) and Conakry (n = 2) were identified by the field teams, and further sampled for LASV RT-PCR as per Ministry of Health National Strategy guidelines in the case of VHF suspicion even in the absence of symptoms.
cord-326319-3538jmqd	2018	title: Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). At 14 dpv, IBV-specific antibody levels in birds immunized with subunit vaccines rHBM-S1-N, rHBM-S1, rHBM-N and inactivated vaccine strain H120 started to rise (p > 0.05). At 14 dpv, IBV-specific antibody levels in birds immunized with subunit vaccines rHBM-S1-N, rHBM-S1, rHBM-N and inactivated vaccine strain H120 started to rise (p > 0.05). Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens
cord-326614-cik3ino6	2020	These trials include a variety of viral targets, vaccine platforms, and adjuvants to boost the immune response to vaccination. Another vaccine utilized the full-length H5 HA protein in an oral recombinant adenovirus type 4 (Ad4) vectored vaccine, Ad4-H5-Vtn. Three clinical trials have enrolled 313 participants between 18 and 49 years of age to investigate this avian H5 influenza vaccine. Although results for the phase II trial have not been posted, a press release from Novavax stated that NanoFlu induced superior HAI antibody responses against homologous and drifted strains compared to the seasonal influenza vaccine. Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: Study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: A phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults
cord-328042-e1is656g	2020	The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits, followed by reverse transcription and quantitative PCR detection. Comparable viral RNA detection sensitivity and specificity were obtained by fluorescent and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) using a primer set targeting the N gene, as well as RT-qPCR using a primer set targeting the E gene, showing that the RNA extraction protocol presented here can be combined with a variety of detection methods at high throughput. Here, we show that the magnetic bead-based protocol yields RNA extracts comparable to the commercially available QIAcube viral RNA extraction kit, as determined by the commonly applied detection methods RT-qPCR and reverse transcription loop-mediated isothermal amplification (RT-LAMP) [16] .
cord-328259-3g4klpyg	2020	Despite the overrepresentation of dsRNA viruses, our results show that Santiago''s sewage RNA virosphere was composed mostly of unknown sequences (88%), while known viral sequences were dominated by viruses that infect bacteria (60%), invertebrates (37%) and humans (2.4%). Viral sequences identified as Partitiviridae-like viruses included in the "unclassified RNA viruses ShiM-2016" category in the NCBI taxonomy (~25% abundance; Figure 2B ) and Totiviriade family were also highly abundant in treated and untreated sewage samples from the EU [5, 7] . Therefore, the abundance of these viruses in the Trebal metagenome can expand the known sequence space associated with this family (only 10 genomes are currently available in the NCBI database) and contribute to a better understanding of the bacteriophage biology related to RNA genomes. Taken together, our results show that metagenomic surveys of RNA viruses in sewage samples and the use of HMMs could uncover extraordinary viral diversity through the detection of remote homologs in these human-impacted environments.
cord-330475-mameyzih	2014	Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. The B23.1-DsRed fusion protein was used to tag the nucleolus, so we could analyze nucleolar localization properties and colocalization in cotransfected cells by live cell imaging (direct fluorescence) or confocal microscopy. These expression plasmids were transfected into Vero E6 cells, the nuclear was stained with DAPI at 24 h post-transfection indicated that amino acids 148-220 directed AcGFP to the cytoplasm and nucleus and had a subcellular localization similar to AcGFP.
cord-330767-jja2wcfz	2019	Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). In previous studies, it has been shown that the transport of GhV G to the cell surface is significantly reduced compared to NiV G and that the majority of the GhV G protein accumulates in the endoplasmic reticulum (ER), suggesting that the amount of surface-expressed GhV G is not efficient enough to trigger conformational changes in the F protein that are required to acquire the fusion-active form of F [35, 36] . However, whereas the glycoproteins of NiV and HeV induce cell-to-cell fusion in a broad variety of cells from different host species, syncytium formation upon expression of GhV F and G proteins is restricted to certain bat cells [32] [33] [34] [35] .
cord-331094-22366b81	2020	We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. After the initial screening, we identified apilimod, emetine, amodiaquine, obatoclax, homoharringtonine, salinomycin, arbidol, posaconazole and nelfinavir as compounds that rescued virus-infected cells from death (AUC from 285 to 585; Table S1 ). We next profiled transcriptional responses to nelfinavir, amodiaquine or both drugs in virus-or mock-infected Vero-E6 cells at 24 h. Anti-SARS-CoV-2 activity of safe-in man broad-spectrum antivirals in Vero-E6 cells. Here, we found that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine or homoharringtonine were synergistic against SARS-CoV-2 in Vero-E6 cells. Thus, the amodiaquine and nelfinavir combination could result in better efficacy and decreased toxicity for the treatment of SARS-CoV-2 and perhaps other viral infections. Transcriptomic analysis of mock-and SARS-CoV-2-infected Vero-E6 cells treated with nelfinavir, amodiaquine or both drugs.
cord-331414-i0oxm5mr	2020	To examine this, GFP was inserted into TC-83, a live-attenuated vaccine for the alphavirus Venezuelan equine encephalitis virus, as well as a low-fidelity variant of TC-83, and passaged until fluorescence was no longer observed. To examine reporter gene stability, three independent replicates of TC-83 GFP and low-fidelity TC-83 GFP were passaged 10 times on Vero cells using an approximate MOI of 0.5 ( Figure 1A ). All three TC-83 GFP replicates contained deletion variants present at a low frequency that were able to selectively remove the GFP reporter gene by passage 10 (Figure 2A) . To better understand the mechanisms underlying the conserved removal of the low-fidelity TC-83 GFP gene, M-fold was used to determine the RNA secondary structure of the virus genome ( Figure 4C-E) . To characterize the role of RNA structure of the virus genome in RNA recombination site selection, we modeled the three most common deletions that occurred at high levels during low-fidelity TC-83 GFP passaging.
cord-332165-31tbc31x	2019	In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors. This concept of targeting multiple, symmetric receptor binding sites by multivalent inhibitors is also applicable for many viruses, since viral capsids are often icosahedral and, therefore, highly symmetric structures. Many members of the polyomavirus family bind sialic acid-based glycans using their VP1 proteins, so the binding sites on individual pentamers are always linked by local five-fold symmetry (Figure 4a , TSPyV). The glycooligopeptide-VP1 complex structures displayed a similar ligand binding mode that was reported for sialic acid in an earlier study [50] and showed, for the compounds, that the linker between the ligand and the scaffold occupies the space that is usually targeted by the natural glycan receptor moieties (Figure 5a,b, right) .
cord-332576-pd62s65y	2017	This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. The expression of EGFP and viral proteins as well as the synthesis of positive-and negative-sense RNA subgenomes in MJ-47-reated infected cells were determined using fluorescent microscope, immunofluorescent staining and real-time RT-PCR assays, as described above. Real-time RT-PCR and immunofluorescent staining demonstrated JEV-EGFP replicon-driven viral positive-and negative-sense RNA genomes were synthesized, as well as replicon-driven EGFP and viral non-structural proteins being expressed in the packaging cell line (Figures 3 and 4) . Real-time RT-PCR and immunofluorescent staining demonstrated JEV-EGFP replicon-driven viral positive-and negative-sense RNA genomes were synthesized, as well as replicon-driven EGFP and viral non-structural proteins being expressed in the packaging cell line (Figures 3 and 4) .
cord-332915-4o2dsf56	2018	We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. In this study, we established a cold-adapted IBV (BP-caKII), and we characterized its pathogenicity in embryos and chickens, tissue tropism, and persistence of infection. We applied a premature reproductive tract pathogenicity model to the differentiation of the pathogenicity of IBVs and performed comparative genomics to shed light on the genetic background of the embryo adaptation of K2 and the cold adaptation of BP-caKII. To test virus titer and embryo pathogenicity, BP-caKII was inoculated into 10-day-old SPF embryonated eggs (Valo Biomedia) via the allantoic cavity route and incubated at 37 • C for 48 h. SNU9106 was passaged 20 times through three embryonated eggs by inoculating allantoic fluid with high virus titer, and BP-caKII was established. SNU9106 was passaged 20 times through three embryonated eggs by inoculating allantoic fluid with high virus titer, and BP-caKII was established.
cord-334027-xhfmio7k	2019	No demonstrable pathologic effects noted during infection of three bat species [big brown bats (Eptesicus fuscus), little brown bats (Myotis lucifigus) and Mexican free-tailed bats (Tadarida brasiliensie mexicana) with various strains of JBEV or St. Louis encephalitis virus (SLEV) [69] . While experimental data demonstrated that some bat species can sustain JBEV infections and support mosquito-borne transmission of this virus, the epidemiological significance of these observations in the field remains unclear. To truly elucidate the role of bats as reservoirs for arboviruses, field surveillance studies documenting natural infection and transmission dynamics among vector and vertebrate species must be supplemented with experimental infections to characterize viremia profiles and infectiousness to vectors, virus-induced pathology, and immune kinetics following infection. The isolation of Marburg virus from Egyptian rousette bats in Uganda in addition to experimental infections demonstrating viremia and shedding in the absence of overt pathology support the role of this bat species as the reservoir for Marburg virus [6, 7, 208] .
cord-334134-fhie2m3u	2012	We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). These results together with the antiviral effect of poly I:C (Figure 3 ) suggested that the protective role of TLR3 against coronavirus infection in J774A.1 macrophages may be mediated by type I IFN. We hypothesized that the differential effect of TLR ligands on MHV production is due to their variable ability to induce type I IFN crucial for triggering an "antiviral state" and protecting cells from virus infection [26, 38] . In the present study prestimulation of J774A.1 macrophages with poly I:C, a potent type I IFN inducer, resulted in a strong IFN-β response that triggered antiviral immunity and protected macrophages from MHV infection before and after virus adsorption.
cord-334560-1j9zmuub	2012	Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. However, for reasons that are not entirely clear, this type of study has not been successful in identifying cell surface proteins that directly interact with EBOV GP to mediate virus entry [41, 42] . However, as both of these regions can be deleted from EBOV GP 1 without loss of viral transduction efficiency [16, [50] [51] [52] , it is likely that C-type lectins increase filovirus attachment to cells rather than serving as cellular receptors that mediate internalization of the virus into endosomes [53] .
cord-334855-s0ci3r8w	2019	Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. The expected response of the emetine-obatoclax drug combination on the viability of FLUAV-and mock-infected RPE cells was calculated using Bliss reference model [29] . After the initial screening, we identified four compounds (obatoclax, emetine, niclosamide and ganciclovir) that at none-cytotoxic concentrations rescued cells from virus-mediated death (Figure 2A) . Table S1 : Compounds, their suppliers and catalogue numbers; Table S2 : Developmental status of broad-spectrum antivirals used in the study; Table S3 : Human viruses and associated diseases; Figure S1 : The expected response of the emetine-obatoclax drug combination on the viability of FLUAV-and mock-infected RPE cells, as measured with the CTG assay using the Bliss reference model; Figure S2 
cord-335279-cfv18qn0	2020	With this Special Issue, which assembles a collection of communications, research articles, and reviews, we intend to explore our understanding of a panel of equine viruses, looking at their pathogenicity, their importance in terms of welfare and potential association with diseases, their economic importance and impact on performance, and how their identification can be helped by new technologies and methods. The authors highlight the potential protective role of eqMx1, which primarily targets the virus nucleoprotein (NP), against the transmission of new IAVs in horses (i.e., eqMx1 could only inhibit the polymerase activity of IAVs of avian and human origin but remained inactive against the equine IAVs tested). To date, equine influenza virus remains one of the most important respiratory pathogens of horses worldwide, with a potential damaging impact on the equine industry, as clearly illustrated in 2007 in Australia and in 2019 in Europe [20, 21] .
cord-335567-ssnvr6nj	2015	In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. In recent years six new human respiratory viruses have been reported including human metapneumovirus (hMPV) [16] , bocavirus and four new human coronaviruses including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), HCoV-HKU1 and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients
cord-335614-qh98622y	2019	These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout. The results of PCA and OPLA-DA analysis showed that there was an obvious separation between the content of the Con and Dis groups, revealing significant changes in the concentrations of metabolites in the kidney induced by NIBV infection. In addition, the transcriptomic analysis showed that NIBV infection also activated the RIG-I-like receptor signalling pathway (Figure 3f , signal 2), which included the transcriptional upregulation of genes such as MDA5, IPS-1, TRAF3, and IκB. In the present study, the ABCG2 mRNA was downregulated in the model group chicken kidneys, partially explaining the significantly increased uric acid levels caused by NIBV infection.
cord-336536-ie5ok0lz	2020	A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice. To identify the potential virulence determinant, sequences of NR-49129, NR-49130, NR-49131 and CA/14-4231 were aligned to reveal conserved genetic changes that we defined as nucleotides in 5 -UTR and amino acids in the coding region that are present only in the non-pathogenic strain but not in pathogenic ones (Supplementary Data S1 and S2). While mutation VP1-L1P allowed a 50% survival of infected mice, VP3-I88V did not cause disease, suggesting its role as major virulence determinant for EV-D68 in this mouse model ( Figure 5E ). While mutation VP1-L1P allowed a 50% survival of infected mice, VP3-I88V did not cause disease, suggesting its role as major virulence determinant for EV-D68 in this mouse model ( Figure 5E ).
cord-337339-0vkigjv2	2020	We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients. Moreover, transgenic mice expressing human ACE2 represent a lethal SARS-CoV-2 infection model resulting in significant weight loss and permitting robust virus replication in the respiratory tract including the lungs [20] . In contrast to SARS-CoV-2 titers, histopathological changes differed markedly between young and aged Syrian hamsters over time: younger animals launched more severe reactions at early time points after infection, while lesions and inflammation in the lungs became more pronounced and widespread at later time points in the elderly. Based on the data presented here, we propose that comparative preclinical assessments of SARS-CoV-2 vaccines and other treatment options in young versus aged hamsters may yield valuable and relevant results, as this small animal model appears to mimic age-dependent differences in humans.
cord-337707-xbwilp1w	2015	title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. Based on a bootscan analysis of the complete genome of the 3 HCoV-OC43s belonging to the circulating genotypes B, C, and D, it was assumed that a hot spot was likely located between the nsp12 and S genes, more precisely at the nsp12/nsp13 junction. This study focuses on the sequences of the nsp12, S, and N genes of 15 HCoV-OC43s detected in respiratory specimens sampled from 2001 to 2013. In this study, all HCoV-OC43s including the VR759 prototype strain are associated with three accession numbers in GenBank, for nsp12, S, and N genes ( Table 1 ).
cord-338436-0z828org	2020	Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects.
cord-338589-1ent68fx	2020	The ensemble docking and characterization work described in this article demonstrates the multifaceted features of the SARS-CoV-2 M(pro) active site, molecular guidelines to improving binding affinity, and ultimately the optimization of drug candidates. After optimization efforts using the design guidelines developed from the molecular docking studies, the average docking score of the parent compounds was improved by 6.59 −log(10)(Kd) in binding affinity which represents an increase of greater than six orders of magnitude. The results of molecular dynamic (MD) simulation of cinanserin-optimized compounds CM02, CM06, and CM07 revealed that CM02 and CM06 fit well into the active site of SARS-CoV-2 M(pro) [Protein Data Bank (PDB) accession number 6LU7] and formed strong and stable interactions with the key residues, Ser-144, His-163, and Glu-166. The use of multiple conformations when using docking will assist in the prediction of new antivirals agents targeting SARS-CoV-2 M pro as the diversity of accessible variations can produce distinct binding poses for an inhibitor compound.
cord-338811-2bi2edcw	2020	To define the dynamic process of enterovirus membrane remodeling of major secretory pathway organelles, we have developed plasmid-based reporter systems that utilize viral protease-dependent release of a nuclear-localized fluorescent protein from the endoplasmic reticulum (ER) membrane during infection, while retaining organelle-specific fluorescent protein markers such as the ER and Golgi. To monitor enterovirus infection in real-time, we adapted cell-based reporter methodologies previously used for flaviviruses and hepatitis C virus that rely on viral protease cleavage-dependent translocation of a membrane-anchored cytoplasmic fluorescent proteins to the nucleus [27] [28] [29] . CVB infection of RepER expressing U2OS cells resulted in a clear translocation of GFP-NLS reporter to the nucleus and eventual dispersal due to cell lysis, while the mCherry-KDEL was maintained in the membranous structure of the ER (Video S1 and Figure 2a) . Live-cell imaging of CVB infected cells expressing these reporters allowed for the real-time visualization of virus-induced changes to the host cell, including the collapse of the peripheral ER network and loss of Golgi integrity.
cord-338973-73a7uvyz	2020	After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections.
cord-339752-o6atz33c	2020	According to a report based on 72,314 cases (test confirmed cases: 44,672 (62%) from the Chinese Center for Disease Control and Prevention, 81% of COVID-19 patients have cold-like symptoms and mild pneumonia, 14% have severe respiratory inflammation, and 5% have critical conditions including respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Similar to SARS (severe acute respiratory syndrome, [2002] [2003] coronavirus (SARS-CoV) [3] , SARS-CoV-2 primarily uses the S protein to invade host cells through ACE2, an enzyme which is known to be important in the renin-angiotensin-aldosterone system (RAAS) [4, 5] . Since TMPRSS2 plays a very important role in SARS-CoV-2 cell entry and ACE2 dysfunction, blocking the activity of TMPRSS2 should be the primary strategy for preventing severe and critical conditions of COVID-19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)
cord-341138-mxjsp3cm	2016	title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. The transspecies transmission of the gibbon ape leukaemia virus (GaLV) and the koala retrovirus (KoRV) is a prime example of a transmission that is still not yet fully understood. Searching for the precursor virus, retroviruses related to KoRV and GaLV have been described in rodents such as South East Asian mice (e.g., Mus caroli [9, 10] and Mus dunni [11] ), as well as in two subspecies of Melomys burtoni in Australia and Indonesia [12, 13] . The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: A novel type C endogenous virus related to gibbon ape leukemia virus
cord-341968-uc8i9h0m	2019	A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Like other enveloped viruses that rely on surface glycoproteins for binding and fusion, coronaviruses have the Spike (S) protein, which is cleaved by proteases during virion biosynthesis, as well as during entry into target cells [53] . The location of furin and related PCs in the vesicles of the constitutive protein secretion pathway, where viruses are assembled during morphogenesis or disassembled during cell entry, explains why a diversity of virus types have evolutionarily converged to depend on PCs. Viruses also use other types of proteases for the proteolytic regulation of the binding and fusion functions; however, proteases are restricted to specific cell types, which limits the range of the viral infection, so when some viruses mutate and acquire PC reactivity, they may expand their cell tropism and become more pathogenic.
cord-342130-eo4le4v3	2019	title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. Double-membraned autophagosomes-like vesicles were detected in PDCoV-infected cells at 12 hpi and increased thereafter. In summary, we demonstrate and elaborate some novel, in vitro characteristics of the life cycle of PDCoV, including replication kinetics in cultured cells, cellular ultrastructure, virion morphology, and possible induction of autophagy, mainly by means of EM observation. In summary, we demonstrate and elaborate some novel, in vitro characteristics of the life cycle of PDCoV, including replication kinetics in cultured cells, cellular ultrastructure, virion morphology, and possible induction of autophagy, mainly by means of EM observation.
cord-342739-iy9vjpuh	2020	In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. The most common adverse obstetrical outcomes associated with maternal pneumonias from all causes include This newly recognized coronavirus, producing a disease that has been termed COVID-19, is rapidly spreading throughout China, has crossed international borders to infect persons in neighboring countries, and humans infected by the virus are travelling via commercial airlines to other continents. Pregnant women may develop severe disease and fatal maternal and/or fetal outcomes as a result of MERS-CoV infection; however, little is known of the pathophysiology of this infection during pregnancy.
cord-342923-prgorr3d	2018	title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection. Previous studies have demonstrated hnRNP A1 could interact with N proteins of SARS Coronavirus and mouse hepatitis virus (MHV) [14, 19] . Our previous work has proved that hnRNP A1 underwent different regulations in jejunum tissues of piglets infected with PEDV virulent strain and its attenuated strain [20] . The beads were then washed with IP lysis buffer five times and boiled in sample buffer, and the proteins were subjected to SDS-PAGE, followed by immunoblotting analysis with anti-Flag PAb or anti-hnRNP A1 PAb. CCL-81 cells grown on coverslips were infected with PEDV YN144 strain, YN13 strain and CV777 strain, respectively, at a multiplicity of infection (MOI) 0.001.
cord-343690-rafvxgx1	2012	Although FIV can cause an acquired immunodeficiency syndrome in cats ("feline AIDS") comparable to human immunodeficiency virus (HIV) infection in humans, with increased risk for opportunistic infections, neurologic diseases, and tumors, in most naturally infected cats, FIV does not cause a severe clinical syndrome. Experimental FIV infection also progresses through several stages, similar to HIV infection in people, including an acute phase, a clinically asymptomatic phase of variable duration, and a terminal phase sometimes called "feline acquired immunodeficiency syndrome" ("AIDS") [18, 19] . Of 8642 FeLV-infected cats presented to North American Veterinary Teaching Hospitals, various co-infections (including FIV infection, feline infectious peritonitis (FIP), upper respiratory infection, hemotropic mycoplasmosis, and stomatitis) were the most frequent findings (15%), followed by anemia (11%), lymphoma (6%), leukopenia or thrombocytopenia (5%), and leukemia or myeloproliferative diseases (4%) [20] . An early defect in primary and secondary t cell responses in asymptomatic cats during acute feline immunodeficiency virus (fiv) infection
cord-345472-qrddwebe	2020	A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. (1), degranulation (2), respiratory oxygen species (ROS) production (3), and the release of neutrophil extracellular traps (NETosis) (4) are associated with increased lung inflammation, systemic fever, mucus hypersecretion, airway obstruction, and epithelial cell death. Excessive neutrophil-derived inflammatory cytokine production (1), degranulation (2), respiratory oxygen species (ROS) production (3), and the release of neutrophil extracellular traps (NETosis) (4) are associated with increased lung inflammation, systemic fever, mucus hypersecretion, airway obstruction, and epithelial cell death. Unlike wild-type (WT) control mice, plasmacytoid dendritic cell (pDC)-depleted, Toll-like receptor (TLR)7-deficient, or interferon regulatory factor (IRF)7-deficient neonatal mice develop severe pathology, characterised by increased neutrophilia and lung inflammation in response to acute PVM infection [80] [81] [82] .
cord-345651-admlzeu4	2019	Using a novel approach, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems efficiently and rapidly rescued another recombinant virus with a 224-amino-acid deletion in the N-terminal domain of the TGEV Spike gene (S_NTD224), which is analogous to the N-terminal domain of porcine respiratory coronavirus. Homologous recombination was then performed using the ClonExpress II One Step Cloning Kit (Vazyme, Nanjing, Jiangsu, China) according to the manufacturer''s instructions using 200 ng of recycled linearized pTGEV-GFP BAC, 45 ng of PCR products of S_NTD and two pairs of primers (rec-672SF/δS-NTDR and rec-672SR/δS-NTDF) ( Table 2) . To construct an infectious clone of TGEV, six overlapping cDNA fragments designated A to F were generated by reverse transcriptase PCR (RT-PCR) using total RNA extracted from PK-15 cells infected with TGEV WH-1 ( Figure 1A ,B). Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus
cord-346836-6jyv0q5e	2011	RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. RVFV infection in humans primarily causes a self-limiting febrile illness; however, some patients develop hemorrhagic fever, neurological disorders, or blindness after the febrile period [5, 7, 8] . Inbred rat strains mimic the disparate human response to rift valley fever virus infection Clinical, virological and serological response of the west african dwarf sheep to experimental infection with different strains of rift valley fever virus
cord-347053-m5m4zgfy	2020	wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of proand anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. The cytopathic effect of H1N1pdm09 included damage to the airway epithelium, the induction of innate immune responses including the expression of pro-and anti-inflammatory cytokines and chemokines and antiviral genes and proteins, consistent with pulmonary host defense. Key genes upregulated in our H1N1pdm09 in vitro challenge model, mimic the innate immune and inflammatory response in human patients in vivo infected with the 2009 pandemic IAV. The more than 350-fold induction of the antiviral-encoding RSAD2 (viperin) gene in our pandemic IAV-infected wdNHBE cells confirms the antiviral response of the airway epithelium in vitro. The disruption of the airway epithelium by IAV H1N1pdm09 and poly(I:C), plus the induction of the innate immune response and antiviral, and pro-and anti-inflammatory genes demonstrated the viability of this model to investigate pandemic influenza.
cord-347362-e4paw26n	2020	The aim of this prospective study was to determine prevalence and potential risk factors of feline coronavirus (FCoV) shedding. Four consecutive fecal samples of 179 cats from 37 German breeding catteries were analyzed for FCoV ribonucleic acid (RNA) by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). Therefore, the aim of this study was to determine the prevalence of FCoV shedding in German breeding catteries and to evaluate associated risk factors. The number of cats per cattery, breed, hygiene management, husbandry conditions and outdoor access were not significantly associated with FCoV shedding in this population (Tables 4 and 5 ). Univariate risk factor analysis in the present study suggested that breed and the number of cats in the household had a significant influence on the prevalence of FCoV shedding, but these results have been distorted by the effect each breeder has on hygienic conditions and the risk of infection within their cattery.
cord-348968-0yoq0geu	2020	The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. In this study, IDV was used as a representative BRD-associated virus to examine the feasibility of using metagenomic sequencing for detection of viruses in clinical bovine respiratory samples. The proportion of viral reads per sample was 0.1% to 18.4% (Nanopore, WIMP analysis) compared to 0.03% to 3.1% for the previously generated MiSeq data; however, with both sequencing approaches, the majority of reads obtained were identified as host-derived or other (bacteria, fungi, unclassified) ( Figure 3 ). Taken together our results demonstrate the potential of metagenomic sequencing on the Illumina MiSeq and Oxford Nanopore platforms for detection of viruses, including IDV, in clinical samples from naturally infected animals with a wide range of viral loads.
cord-349011-kxhpdvri	2019	Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O''Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. The "Viral Subversion of Host Cell Processes" session also included presentations from the following trainees: Nichole McMullen (Dalhousie University) who reported the unconventional egress mechanisms of non-enveloped reoviruses, Justine Sitz (Université Laval) who described interactions between a human papillomavirus protein and a host DNA repair-specific E3 ubiquitin ligase, and Quentin Osseman (Université de Montréal) who described interactions between respiratory syncytial virus (RSV) and the host autophagy pathway.
cord-349117-xfir3m5p	2020	After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. SARS CoV-2 strain 2019-nCov/Italy wild-type virus (LV), which was handled in a level 3 bio-containment facility (BSL 3), was used as positive control in order to evaluate the spike glycoprotein expression, while a ∆-envelope pseudotype, prepared with the same procedure, was used as a negative control. To verify the expression of the spike protein in the SARS-CoV-2 pseudotypes, the spike was detected by Western blot; sera from convalescent SARS-CoV-2 patients, which have been shown to have a high neutralising titre in microneutralisation with a live virus, were used as the primary antibody, and goat anti-Human IgG as the secondary antibody.
cord-349560-8n65rgfz	2009	The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Creer and co-workers [1] identified at least one potential pathogen in 69% of specimens from adults suffering from lower respiratory tract infections (LRTI, 63% contained viruses, 26% contained bacteria) still leaving a significant diagnostic gap to be filled with so far unidentified pathogenic microorganisms. For this reason, detection of virus-specific antibodies by complement fixation assays, enzyme linked immunosorbent assays (ELISA), or immunofluorescence assays (IFA), all of which are available for established respiratory viruses, is inappropriate for the identification of the etiologic agent causing an acute respiratory tract infection, but useful for retrospective or epidemiological studies. Following the discovery of WUPyV in Australia, the virus was detected in specimens from patients with respiratory tract disease on all continents suggesting a worldwide distribution [10, [29] [30] [31] .
cord-350964-0jtfc271	2018	In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Nucleic acid that was extracted from liver samples of 157 bats (29 species; Table S1 ) and 470 rodents (six species) was screened for pegivirus and human hepatitis B, C, E viruses and their homologues ( Table 1 ) by nested and semi-nested PCR assays with degenerate primers.
cord-351228-hpo8bboi	2013	Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. Nevertheless, a major conclusion of most series documenting outcomes in patients with PBC following liver transplantation is that CsA is associated with a lower incidence of recurrent disease [10] [11] [12] [13] [14] [15] [16] 18] . Other agents, such as hepatitis C virus (HCV) rely on cyclophilin A interactions with viral components of the replication complex to produce RNA transcripts, a process also blocked by CsA [64] [65] [66] [67] [68] [69] [70] [71] . Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis
cord-351365-dc9t3vh3	2016	Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. Figure 1 provides an overview of a selection of RNA viruses against which RBV was shown to be active: hepatitis C virus (HCV, Flaviviridae), dengue virus (DENV, Flaviviridae), respiratory syncytial virus (RSV, Paramyxoviridae), influenza A and B virus (Orthomyxoviridae), chikungunya virus (CHIKV, Togaviridae), poliovirus (Picornaviridae), Hantaan virus (Bunyaviridae), and Lassa virus (Arenaviridae) [28, 29] ( Figure 1 ). Furthermore, mechanisms on the virus itself were described by inhibition of the capping efficiency, the viral polymerase, and a mutagenic effect on newly synthesized RNA genomes. A Mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients
cord-351377-xorj8tnz	2018	Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. While one piglet in the PEDVPT-P96 group showed intermittent loose diarrhea (score = 1) and viral shedding at 6 to 11 days post-inoculation (DPI) with the peak viral titer of 1.45 ± 3.24 log 10 RNA copies/mL at 8 DPI (Figure 4) , no evidence of PEDV-associated clinical signs and fecal viral shedding were demonstrated in both iPEDVPT-P96 and mock groups.
cord-351489-tzmev77c	2020	They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. In this primary screening, chloroquine, lopinavir, and remdesivir which were recently reported to have anti-SARS-CoV-2 activity, exhibited about 1.3-2.0 log10 copies/mL reduction in viral RNA load ( Figure 1 ). In comparison, recombinant IFN-β demonstrated the most potent anti-SARS-CoV-2 activity, with Avonex (IFN-β1a), Rebif (IFN-β1a), and Betaferon (IFN-β1b) each achieving about 3 log10 copies/mL reduction in viral load. In our primary screening using a fixed antiviral agent concentration and virus inoculum, we identified recombinant IFNs and lipogenesis modulators to be the most potent anti-SARS-CoV-2 agents among 22 broad-spectrum antivirals.
cord-351760-698voi9y	2018	The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. In vivo study demonstrated that prophylaxis with m336 reduced virus titers in the lung of rabbits infected with MERS-CoV [15] , and m336 also provided transgenic mice expressing human DPP4 with full prophylactic and therapeutic protection from MERS-CoV [16] . A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection Passive Transfer of a Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV
cord-351955-9l4786lb	2009	Complete structural (S, E, M, N) and accessory (3a-c and 7 a, b) gene sequences were obtained from diseased omentum of the four related cats that died of FIP and the isolates designated were FIPV-UCD11, 12, 13 and 14 ( Table 1 ). The coronavirus isolated from Lucy''s feces (designated FECV-UCD3) had an intact (i.e., wild type or non-deliterious) 3c and its sequence was otherwise 99% identical to the sequence of FIPV-UCD14 found in her diseased omentum. FECV-UCD4, was most closely related to the FIPV isolated from Lucy and was 99.7% related to the consensus nucleotide sequences of coronaviruses obtained from the four related FIP cats ( Figure 1 , Table 2 ). The 3c gene sequence of the fecal virus of cat 388406 was intact and ≥99% related to the FIPV found in diseased tissue ( Table 2 ).
cord-352007-3djwbivp	2020	Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. The results show that the mRNA level and protein level of Beclin1 were significantly reduced in RD cells; moreover, knockdown of BECN1 inhibited EV71 replication ( Figure 3A,B) . Our group has previously reported several host factors regulating EV71 replication; for example, SIRT1 can inhibit EV71 replication and RNA translation by interfering with the viral polymerase and 5 UTR RNA [57] , and PolyC-Binding Protein 1 interacts with 5 -untranslated region of EV71 RNA in membrane-associated complex to facilitate viral replication [58] . In FMDV (Foot-and-mouth disease virus)-infected cells, the largest viral protein in the replication complex, 2C, would bind to Beclin1 to prevent the fusion of lysosomes to autophagosomes, allowing for virus survival [35] .
cord-352527-eeyqh9nc	2019	A number of MERS vaccines have been developed based on viral RBD, including nanoparticles, virus-like particles (VLPs), and recombinant proteins, and their protective efficacy has been evaluated in animal models, including mice with adenovirus 5 (Ad5)-directed expression of human DPP4 (Ad5/hDPP4), hDPP4-transgenic (hDPP4-Tg) mice, and non-human primates (NHPs) [88] [89] [90] [91] [92] [93] [94] . Receptor usage of a novel bat lineage C Betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human dipeptidyl peptidase 4 binding Recombinant receptor-binding domains of multiple Middle East respiratory syndrome coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-CoVs and antibody escape mutants A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV
cord-352619-s2x53grh	2020	Genomes from several families of circular Rep-encoding single-stranded DNA viruses (CRESS-DNA viruses) are part of the phylum Cressdnaviricota [22] and have been identified in fecal samples of other mammals, including domestic cats [23, 24] , bobcats, African lions [25] , capybaras [26] , and Tasmanian devils [27] . Here we used a metagenomic approach to identify novel circoviruses in the feces of two species of Sonoran felids, the puma and bobcat; although not endangered, knowledge of viral threats facing these species could help prevent future population decline, as well as indicate potential threats to the endangered ocelot and jaguar. Based on the species-demarcation threshold for circoviruses which is 80% genome-wide identity [28] , both of these belong to a new species which we refer to as Sonfela (derived from Sonoran felid associated) circovirus 1. As the viral genomes were derived from scat samples, the circoviruses could have infected the bobcat prey species or the felids themselves or be environmentally derived.
cord-353365-ujz5nkk3	2020	The medical military command implemented testing of all Belgian soldiers for SARS-CoV-2 viral load and antibodies, two to three days before their departure on a mission abroad or on the high seas, and for specific missions immediately upon their return in Belgium. The SARS-CoV-2 outbreak in a Belgian military education and training center in Maradi, Niger, was characterized by mild symptoms in five soldiers and asymptomatic infection in two soldiers (one trainer), both having a viral load, as diagnosed upon their timely return to Belgium. The SARS-CoV-2 outbreak in a Belgian military education and training center in Maradi, Niger, was characterized by mild symptoms in five soldiers and asymptomatic infection in two soldiers (one trainer), both having a viral load, as diagnosed upon their timely return to Belgium.
cord-353609-no3mbg5d	2011	Conducting viral surveillance in animal reservoirs and invertebrate vectors can help explain circulation within host species; observed patterns of zoonotic transmission; and even allow for the prediction of periods of increased risk of zoonotic transmission (e.g., Rift valley fever and rainfall [25] ; West Nile virus (WNV) and American robin (Turdus turdus) migration [26] ; as well as hantavirus in mice [27, 28] ). Globalization, host ecology, host-virus dynamics, climate change, and anthropogenic landscape changes all contribute to the complexity of zoonotic viral emergence and disease, and create significant conservation and public health challenges. While the lasting efficacy of wildlife vaccination efforts has yet to be demonstrated with either endangered species or in breaking the transmission cycle of human pathogens, an increasing number of researchers are drawing attention to systems where it seems feasible [99, 103] ; demonstrating that intricate knowledge of host and virus ecology can greatly reduce the amount of vaccine coverage that is necessary to control these viruses.
cord-354068-4qlk6y7h	2012	Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge.
cord-354738-4rxradwz	2014	In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. Various publications reviewed bats globally as carriers and potential reservoir hosts of human-pathogenic and zoonotic viruses [3] [4] [5] [6] [7] [8] [9] [10] , while hardly anything is known about human-pathogenicity of European bat viruses apart from lyssaviruses. Similar to the case of the LLOV filovirus, virus isolates and prevalence studies in both humans and bats could improve knowledge and clarify their zoonotic potential. Sero-prevalence studies should be conducted on the orthoreoviruses isolated from European bats, especially as a closely related virus was detected in a diseased child in Slovenia [83] . Other bat viruses detected by using molecular techniques should be isolated (e.g., MERS-like CoV or Bat Bunyavirus) to allow for characterization and follow-up sero-prevalence studies.