cord-000346-9b6yz3f4 2011 In order to obtain two complementary views of the infection kinetics for the A/Brisbane/59/2007 WT and H275Y mutant strains, virus growth over time was observed in two different in vitro systems: the viral plaque assay and the multiple-cycle viral yield assay. We are left then with two experimental measures -the viral titer growth rate and the plaque velocity -whose values may depend on three unknown infection kinetics parameters: the infecting time, t inf ; the latent infection period, t L ; and the infectious lifespan of a cell, t I . To demonstrate this concept using the A/ Brisbane/59/2007 (H1N1) WT and H275Y mutant strains, we have plotted the experimentally-measured values of plaque velocity and viral titer growth rate as functions of the infecting time and latent infection period, using the model dependence determined above ( Figure 6 ). cord-001340-kqcx7lrq 2014 cord-001985-iwfidoer 2016 cord-002608-zn7tm1ww 2017 A CLIP-seq approach was used to screen for candidate sites of interaction between the viral Capsid protein and genomic RNA of Sindbis virus (SINV), a model alphavirus. The data presented in this report indicates that the SINV capsid protein binds to specific viral RNA sequences in the cytoplasm of infected cells, but its interaction with genomic RNA in mature extracellular viral particles is largely non-specific in terms of nucleotide sequence. This report details our efforts to identify and characterize the sites of interaction between the viral capsid protein and the genomic RNA using the model alphavirus Sindbis virus (SINV). C) The infectivity of the individual SINV C:R interaction site mutants and parental wild type virus as reported as the ratio of total particles per infectious unit as determined using BHK-21 cells. cord-003045-r707jl16 2018 The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups. Available online at: https:// www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/ licensedproductsblas/blooddonorscreening/infectiousdisease/ucm080466.htm Abbreviations: HBV, Hepatitis B virus; HCV, Hepatitis C Virus; HERV K113, Human Endogenous Retrovirus K113; TCGA, The Cancer Genome Atlas; HCC, Hepatocellular carcinoma; NAFLD, nonalcoholic fatty liver disease; Hep B, Hepatitis B; Hep C, Hepatitis C; HepB + HepC, coinfected with both Hepatitis B and C virus; HBsAg, Hepatitis B surface antigen; HBeAg, Hepatitis B type e antigen; NGS, next-generation sequencing; RNA-seq, whole transcriptome sequencing; BAM, Binary version of Sequence alignment/map format; CDS, coding sequence; Cox PH, Cox Proportional Hazard; HBx, viral gene X; STS, Sequence-tagged sites; NCBI, National Center for Biotechnology Information; GFF, general-feature-format. cord-004501-guiy89x8 2020 According to the literature data results, namomaterials designed with different shapes and morphologies display numerous advantages for use in antiviral therapy, namely: nanometric size that permits drug delivery through impermeable barriers [88] , large surface area to volume ratios for large drug payloads incorporation [117] and improved efficacy, surface modification and/or backbone functionalization versatility that facilitates cellular membranes passage [118] or enhancing stability and bioavailability [119] , virucidal activity against a series of viruses (HIV, HSV, HBV, etc.) due to biomimetic properties [120] , increased specificity, improved antiviral delivery and controlled drug release to the target [121] through engineered moieties, decrease the emergence of drug resistance, personalized therapy possibility, protection of the drugs and low adverse drug side effects mainly due to the composition. cord-006129-5rog0s98 2012 cord-006450-si5168pb 2012 The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p < 0.01 for each comparison). The variables significantly associated with positive viral tests on univariate analysis were immunosuppression (i.e., HIV infection, corticosteroids >10 mg/day for ≥3 weeks, and/or other immunosuppressive therapy), ground-glass attenuations on chest CT scans, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) ICU stay, and (iii) mechanical ventilation before BAL was performed (p<0.01 for each comparison). This advocates for the systematic use of PCR techniques for viral tests in BALF, in accordance with previous studies [27, 28] , in the situations where viruses may reasonably be suspected (i.e., acute lower tract respiratory disease in immunocompromised patients and/or patients with unexplained bilateral ground-glass attenuations on CT scan). cord-007255-jmjolo9p 2009 The database contains information on the 3 molecular characteristics hypothesized to influence the potential of a virus to cross host species: site of replication (X SR ; whether replication is completed in the cytoplasm or requires nuclear entry), genomic material (X GM ; RNA or DNA), and segmentation of the viral genome (X Seg ; segmented or nonsegmented). Hypothesis testing allowed us to determine how likely it was that the observed patterns were due to chance, whereas model-based prediction allowed us to determine what trait or set of traits was the best predictor of a livestock virus''s ability to infect humans and to estimate the probability that a particular virus species would be able to jump host species, given knowledge of the traits of interest. To examine the magnitude and relative importance of the effects that the 3 molecular characteristics of interest have on the ability of the viral species in the database to infect humans, we developed a set of logistic regression models. cord-009101-376snefs 2015 cord-009577-29u7pdpk 2004 cord-010233-772e35kx 2002 cord-011095-79ce5900 2020 cord-014397-7b88ycv8 1996 cord-015893-e0fofgxq 2011 cord-016475-7ldxvbpz 2006 After influenza virus infection antibodies directed against all major viral proteins can be detected in humans and the level of serum antibodies correlate with resistance to disease (Couch, 2003; Couch and Kasel, 1983; Coulter et al., 2003; Nichol et al., 1998; Potter and Oxford, 1979) . Nevertheless, IKK and NFκB might not only have anti-viral functions as two recent studies demonstrate that influenza viruses replicate much better in cells where NFκB is pre-activated (Nimmerjahn et al., 2004; Wurzer et al., 2004) . Apoptosis is mainly regarded to be a host cell defense against virus viruses (reviewed in: Julkunen et al., 2000; Ludwig et al., 2003; infections since many viruses express anti-apoptotic proteins to prevent this cellular response. Influenza virus-induced NF-kappaB-dependent gene expression is mediated by overexpression of viral proteins and involves oxidative radicals and activation of IkappaB kinase cord-016499-5iqpl23p 2014 A convenience population of 15 healthy children (1-9 years old) without asthma were followed during at least three seasons, and picornaviruses were detected in 5 % of 740 specimens (21 % of infections) not associated with symptoms, The impact of HRV typing and of sampling based only on symptoms. Clinical features and complete genome characterization of a distinct human rhinovirus genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children Comparison of results of detection of rhinovirus by PCR and viral culture in human nasal wash specimens from subjects with and without clinical symptoms of respiratory illness Detection of human rhinovirus C viral genome in blood among children with severe respiratory infections in the Philippines cord-016798-tv2ntug6 2019 cord-018058-n3majqes 2013 Many of the steps that characterize a viral infection were first discovered in experiments with bacterial viruses: such processes include attachment and penetration, the reproduction-cycledependent regulation of gene expression that results in early and late synthesized proteins, and lysogeny, which is associated with the existence of prophages. Besides the importance for tumour virus research, these observations aroused interest in the question concerning the basis of the high susceptibility of newborn animals to viral infections, and suggested investigations on the innate resistance of an organism to infections as well as the time and the causes of its formation. Between 1918 and 1920, a pandemic emerging viral disease, Spanish flu, claimed more than 20 million lives, i.e., more than in the First World War. After cultivation of the virus responsible in embryonated chicken eggs in 1933, their haemagglutinating properties were discovered in 1941 (i.e., their ability to agglutinate red blood cells), thereby laying the basis for the development of haemagglutination tests to detect viruses. cord-018325-k69h9cc5 2019 cord-018430-u3k8pds6 2007 The classification states that "myocarditis is diagnosed by established histological, immunological and immunohistochemical criteria." The Dallas criteria 5 provide consensus-derived histologic criteria: "an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of ischemic damage associated with coronary artery disease." However, many have speculated that less pronounced histologic abnormalities may be present and that additional molecular, immunologic, and immunohistochemical diagnostic criteria can be used productively. 330 These criteria define active myocarditis (see also Fig. 59 .7A) as "an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of ischemic damage associated with coronary artery disease." Furthermore, other causes of inflammation (e.g., connective tissue disorders, infection, drugs) should be excluded. 392 An interesting hypothesis to explain the high frequency of dilated heart muscle disease is the presence of myocarditis in HIV-infected patients with left ventricular dysfunction. The ECG abnormalities suggesting myocardial involvement are present in a high proportion of patients, 414 but clinical evidence of cardiac dysfunction occurs in only 10% to 25% of cases. cord-018526-rz7id5mt 2018 Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies. In humans, intramuscular injections of naked plasmid encoding angiogenic factors (such as VEGF165 or HGF) were used in small numbers of patients with critical limb ischemia and did demonstrate promising clinical efficacy for the treatment of peripheral arterial disease. A meta-analysis of 12 clinical trials (1494 patients total) of local administration of pro-angiogenic growth factors (VEGF, FGF, HGF, Del-1, HIF-1alpha) using plasmid or viral gene transfer by intra-arterial or intramuscular injections showed that, despite promising results in single studies, no clear benefit could be identified in peripheral artery disease patients, irrespective of disease severity [51] . cord-020235-stcrozdw 2012 cord-021146-wdnnjlcw 2020 cord-022156-mm8en4os 2015 Tracheal infections have a signifi cantly lower incidence compared to infections of the upper respiratory tract, with 1-5 % of all children requiring outpatient evaluation for viral croup within the fi rst 3 years of life. In 1958, the fi rst evidence for association between croup and two newly isolated myxoviruses, parainfl uenza virus types 1 and 2, resulted in separation of two categories of cases-mild, requiring only outpatient follow up, and severe, requiring hospitalization [ 12 ] . Among other important viral pathogens causing tracheal infections, RSV was studied in isolates from sentinel practices in England and Wales from 1975 to 1990, during which an increase in mortality, by as much as 60-80 %, was observed in comparison with parainfl uenza and infl uenza viruses [ 13 ] . [ 31 ] studied the clinical courses of croup caused by parainfl uenza and infl uenza viruses to highlight the differences in morbidity caused by the different viral strains in hospitalized children. cord-022196-1tionxun 2013 With most isometric particles and in all complex virions, the capsid encloses another protein structure containing the viral genome, called the core. All animal viruses with tubular nucleocapsids are enveloped, and in these the lipid layer from which glycoprotein peplomers project is probably applied to a protein shell (the membrane protein; see Fig. 1 -1), which may be relatively rigid, as in Rhabdovirus, or readily distorted (as in the myxoviruses) so that in negatively stained electron micrographs the virions appear to be pleomorphic. The RNA viruses that have the largest (single-stranded) genomes, those of the Leukovirus genus, also have a highly complex structure with an envelope enclosing an icosahedral capsid that, in turn, surrounds a tubular nucleocapsid. The conventional physicochemical criteria [(a) nucleic acid: type, strandedness, fragmentation, and molecular weight; (b) virion: shape, size, and symmetry] are suitable for classification at this level of family/genus, perhaps assisted by the serological cross-reactivity of "group" antigens where these have been recognized. cord-022349-z8w1wkm8 2007 cord-022439-8wy7rpqv 2013 cord-023143-fcno330z 2004 Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. cord-023705-3q9yr6np 2014 cord-023731-jqgervt7 2014 Having allocated it to a particular family (e.g., Adenoviridae), one can then go on to determine the species or serotype (e.g., canine Immunodiffusion Antibody neutralizes infectivity of virion; inhibits cytopathology, reduces plaques, or protects animals Antibody inhibits viral hemagglutination Antigen-antibody complex binds complement, which is thereafter unavailable for the lysis of hemolysissensitized sheep red blood cells Antibody-aggregated virions are visible by electron microscopy Antibody labeled with fluorochrome binds to intracellular antigen; fluoresces by UV microscopy Peroxidase-labeled antibody binds to intracellular antigen; colored precipitate forms on adding substrate Enzyme-labeled antibody (or antigen) binds to antigen (or antibody); substrate changes color Radiolabeled antibody (or antigen) binds to antigen (or antibody), e.g., attached to solid phase Antibodies and soluble antigens produce visible lines of precipitate in a gel adenovirus 1) by more discriminating serological procedures. cord-103460-5thh6syt 2020 cord-252763-gy8f1oyt 1995 A total of 106 children below 5 years of age admitted to the Kasturba Medical College Hospital Manipal Karnataka (South India) were investigated over a period of 6 months to determine the aetiologkal role of viruses in acute diarrhoea. 1 " 3 In view of the recent recognition of some viral aetiological agents of acute infantile diarrhoea, we conducted the present study to identify viruses as the causative agents of infantile diarrhoea in Manipal, a place in Coastal Karanataka (South India). One-hundred-and-six children aged below 5 years, suffering from acute watery diarrhoea of less than 4 days'' duration who attended the out patient clinic of paediatric dept of the Kasturba Medical College Hospital, Karanataka, South India were included in the study. Enteric adenoviruses are well established as respiratory viruses and are second to Rotavirus as the most common cause of pediatric viral gastroenteritis. cord-254194-962vynwk 2011 cord-254478-scc9wee0 2020 title: Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. We present findings of an observational cohort study of the temporal profile of viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from posterior oropharyngeal saliva samples and serum antibody responses, dated by symptom onset and correlated with clinical findings. cord-258685-ayek8zbo 2020 Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ''Disease X''. The lysis of viral infected cells by activated innate effector cells and cross-reactive allo-specific memory CTL releases "danger signals" [18] and heat shock proteins (HSP) [19] which chaperone viral antigens (e.g., GRP78, HSP70) [20, 21] into the microenvironment, creating the conditions for "in situ vaccination", which leads to development of viral-specific cellular immunity. Modulating the immune system of elderly individuals through alloantigen priming to provide high titers of non-exhausted Th1/ CTL memory cells that can be non-specifically activated upon encounter with any virus to cause release type 1 cytokines may provide an immediate anti-viral immune response upon viral exposure and could also reinstate responsiveness to viral vaccines [85] . cord-259233-smmhhroe 2016 cord-260554-nao59qx4 2012 cord-262585-5vjqrnwh 2019 cord-262753-jld1ygxt 2019 cord-262776-6k7tcgfs 2004 cord-265900-7lj4bfli 2015 Several proteins encoded by DNA tumor viruses, such as the human papillomavirus (HPV) E6 and E7 proteins [14, 15] and the adenovirus E1B55k/E4orf6 proteins [16] , have been shown to induce the assembly of an E3 ligase complex that contains both viral protein and cellular E3 to catalyze the ubiquitination of p53 and subsequent degradation by the proteasome. In addition to its pro-viral function usurped by viruses as discussed above, the UPS-mediated cellular protein degradation may also represent a host defense mechanism against viral infection. ISG15 and the ISGylation conjugation system represent an important host defense mechanism against infection of a broad spectrum of viruses, including Sindbis virus, Viral interaction with the host ubiquitin-proteasome system (UPS): pro-viral and anti-viral function of the UPS in viral pathogenesis. The UPS, including modification of key signaling molecules involved in innate immunity by ubiquitin or ubiquitin-like modifiers (e.g. SUMO and ISG15), represents an important host anti-viral defense mechanism. cord-266147-s8rxzm0t 2007 Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as α1-protease inhibitor, von Willebrand factor, and protein C. A complete set of measures-and, most particularly, the use of dedicated viral inactivation and removal treatments-has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In the last few years, the complexity of the fractionation process has increased by (a) the introduction of chromatography to isolate new proteins from existing fractions such as cryoprecipitate, cryo-poor plasma, and Cohn fractions; (b) the integration of chromatography to the ethanol fractionation process to increase IgG recovery; and (c) the implementation of dedicated viral inactivation or removal steps. cord-267326-355q6k6k 2018 This study shows that spatial factors (e.g., reservoirs/tributaries, land use) are the main drivers of the viral community structure in tropical freshwater ecosystems. However, up till now, studies of land use impacts on the virome community in freshwater ecosystems are still limited as they mainly rely on traditional methodology (culture-based method or qPCR/RT-qPCR), which focuses on limited human virus targets without considering the whole picture of the viral community in the water environment (Corsi et al., 2014; Lenaker et al., 2017) . Thus, the objectives of this study were to: 1) investigate the overall virome distribution and diversity in diverse freshwater ecosystems (reservoirs/tributaries) in a tropical environment, 2) compare the virome community based on the different land use patterns, 3) assess the extent of human-related pathogenic viruses in surface waters, especially emerging zoonotic and human-related viruses, which may have been undetected before. cord-269194-b1wlr3t7 2015 Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats. With the development and administration of newer drugs that target specific biological processes of HIV, routine and clinical monitoring of viral loads using a real-time quantitative PCR assay continues to be critical to predict treatment failure and early emergence of drug resistance mutations, within a timeframe that would increase subsequent treatment success. cord-270205-fw555w1u 2019 cord-270294-g95skuik 2008 Furthermore, viral etiology studies in pneumonia are difficult to interpret as noninvasive viral detection methods are often considered to be only markers of infection rather than the cause of pneumonia." Clearly, much better knowledge of the potential role of respiratory viruses present in patients with pneumonia is needed. More recently, the introduction of highly sensitive nucleic acid amplification tests (NATs) has dramatically improved our ability to detect multiple viral pathogens such as influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza, and adenovirus. [13] [14] [15] To date, there have been few studies, 5, 7, [9] [10] [11] 16 ,17 reported in patients with pneumonia using NATs to detect viral infection, and these studies have either not included clinical data 7.9.11 or have not tested for all potentially important respiratory viruses in a comprehensive manner.lv-!? cord-270670-cubh9jxc 2006 a Upon infection with an RNA virus (even with a single particle, as depicted here, enlarged about 10 6 times), viral replication leads to a mutant spectrum of related genomes, termed viral quasispecies. As further discussed in the text, in real infections multiple mutant spectra that can amount to a large number of replicating (or potentially replicating) genomes (up to 10 9 or even 10 12 per infected individual) provide highly dynamic mutant repertoire viral yields in cell culture, have been immensely powerful in characterizing the population dynamics of RNA viruses (see references in the reviews by Domingo and Holland 1997; Quiñones-Mateu and Arts 2002; Novella 2003; and the chapters by Quiñones-Mateu and Arts and Escarmís et al., this volume) . Despite these limitations, determination of nucleotide sequence heterogeneities in virus populations using correct reagents and adequate controls has consistently documented that most RNA viruses (and also some DNA viruses) consist of complex mutant spectra, with an average number of 1-100 mutations per genome (Sect. cord-271495-5906wju4 2020 cord-272655-qeojdpez 2015 cord-273019-hbpfz8rt 2018 cord-274080-884x48on 2018 For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. cord-274680-6pui91uu 2020 cord-274749-ji91qq9q 2015 The viruses most frequently detected in children with ARIs include respiratory syncytial virus (RSV), influenza virus (INF) types A and B, adenovirus (AV), parainfluenza virus (PIV), human metapneumovirus (HMPV) and rhinovirus (RV) [3] [4] [5] ; however, the clinical presentations of respiratory tract infections are similar, making it difficult to distinguish between etiologic agents without a laboratory diagnosis [6] . We aimed to document the prevalence of selected viral and bacterial infections among children <5 years of age hospitalized with severe acute respiratory illness (SARI) at selected hospitals in Niger from January 2010 through December 2012. We report the detection rate of selected viral and bacterial pathogens among children <5 years of age hospitalized with SARI in Niger. This study reports the detection rate of viral and bacterial pathogens among children <5 years of age hospitalized with SARI in Niger. cord-274780-fmnro0kw 1981 cord-275683-1qj9ri18 2019 cord-276908-9jthjf24 2020 cord-279716-kxfc4npg 2007 Background Influenza virus was used to characterize the efficacy of a cyclone‐based, two‐stage personal bioaerosol sampler for the collection and size fractionation of aerosolized viral particles. Results Based on qPCR results, we demonstrate that aerosolized viral particles were efficiently collected and separated according to aerodynamic size using the two‐stage bioaerosol sampler. In order to quantify the relative amount of viral particles or fungal spores collected at each stage of the bioaerosol sampler, qPCR was performed in parallel using either serial 10-fold dilutions of cDNA generated from a single dose of non-aerosolized FluMist Ò containing approximately 10 7 TCID 50 per influenza strain or genomic DNA isolated from 10 7 spores. In this study, by aerosolizing FluMist Ò , we demonstrate the recovery of aerosolized viral particles using the bioaerosol sampler and detection of influenza by qPCR. cord-280048-b4dz1lnn 2019 Research on quasispecies has proceeded through several theoretical and experimental avenues that include continuing studies on evolutionary optimization and the origin of life, RNA-RNA interactions and replicator networks, the error threshold in variable fitness landscapes, consideration of chemical mutagenesis and proofreading mechanisms, evolution of tumor cells, bacterial populations or stem cells, chromosomal instability, drug resistance, and conformation distributions in prions (a class of proteins with conformation-dependent pathogenic potential; in this case the quasispecies is defined by a distribution of conformations) [16, 20] . Adaptability of RNA viruses is linked to parameters that facilitate exploration of sequence space: genome size (1.8 to 33 Kb), population size (variable but that can attain an impressive 10 12 individual genomes in an infected host at a given time), replication rate, mutation rate, fecundity (yield of viral particles per cell), and number of mutations required for a phenotypic change (surprisingly low for several relevant traits) (see [49] ). cord-281844-c0uhcatg 2014 cord-281916-v6u5mr2i 2016 cord-286137-4cbh3u3z 2020 In mineral-and vitamin-deficient mice, genetic mutations arise in coxsackie B and influenza virus populations that promote virulence even in well-nourished hosts [36] [37] [38] [39] [40] . Experimental evolution of CA/09 virus through two models of murine obesity resulted in a viral population displaying increased virulence upon inoculation of a wild-type host. Interestingly, arbovirus-infected obese or protein-deficient mice showed higher morbidity but lower viral diversity, and both malnourished models transmitted virus less efficiently, highlighting that the effects of nutrition may vary based on the natural life cycles of viral families [42] . In our studies with influenza virus, we linked the emergence of a more diverse and virulent viral population with blunted interferon responses in obese hosts. Interferon treatment of obese mice restricted the emergence of a diverse quasispecies and attenuated the virulence of the resulting viral population, strengthening the claim that a robust innate immune response restricts subsequent infection severity, possibly through reduced viral replication and acquisition of a genetically diverse viral population [8, 20, 41] . cord-286219-qcx5ehnh 2014 cord-286328-ap0wfjhq 2012 CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes. To further examine the innate immune response to viral infection in children with asthma, we measured nasal aspirate cytokine levels in 16 asthmatic children before and after upper respiratory tract infections. We also examined the effects of upper respiratory tract infection on mRNA levels of selected markers of viral infection, including IFNs. Finally, we evaluated a new method of virus detection using a single polymerase chain reaction-ligation detection reaction (PCR-LDR) multiplex assay. We performed home measurements of respiratory symptoms and collected nasal secretions (for detection of viral RNA by PCR and host biomarkers by PCR and ELISA) on 3 days during a week when children were healthy (not reporting upper respiratory tract infection or asthma symptoms), and again during a week when they experienced cold or flu-like symptoms. cord-286337-qk90xb3a 2018 While the effects of these alterations on risk of secondary bacterial pneumonia have not been studied, potential mechanisms by which these changes might modulate susceptibility to secondary bacterial infections include alterations in the nature and magnitude of the immune response in the host (microbiome on host effects) and facilitating growth of pathogens in the absence of normal commensals (inter-microbial effects). Given the effects of viruses on enhancing bacterial adherence to the epithelium (86) (87) (88) , it is perhaps not surprising that multiple studies of human subjects as well as in animal models have shown that viral infections are associated with increased colonization by potentially pathogenic bacteria (known as "pathobionts"). Another study of patients with 2009 pandemic H1N1 influenza infection revealed that the predominant phyla of the upper respiratory tract (nasal and nasopharyngeal samples) in patients harboring pandemic H1N1 were Actinobacteria, Firmicutes, and Proteobacteria although normal controls were not included; however, the authors suggested that flu is associated with an expansion of Proteobacteria (109) which is generally less abundant in healthy hosts. cord-286843-8qh1pblc 2018 cord-287459-k9x3z2h1 2020 cord-287711-gw8mgg4m 2017 Data from spiking studies quantifying the viral filtration performance of cellulosic filters are detailed, i.e., first, the virus reduction capacity of regenerated cellulose hollow fiber filters in the manufacturing process of blood products and, second, the efficiency of virus recovery/concentration from water samples by the viradel (virus adsorption–elution) method using charge modified, electropositive cellulosic filters or conventional electronegative cellulose ester microfilters. Data from spiking studies quantifying the viral filtration performance of cellulosic filters are detailed, i.e., first, the virus reduction capacity of regenerated cellulose hollow fiber filters in the manufacturing process of blood products and, second, the efficiency of virus recovery/concentration from water samples by the viradel (virus adsorption-elution) method using charge modified, electropositive cellulosic filters or conventional electronegative cellulose ester microfilters. cord-287758-da11ypiy 2020 The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell. cord-287770-oxfnt2n4 2013 title: Safety of snake antivenom immunoglobulins: Efficacy of viral inactivation in a complete downstream process In this article, we used a wide panel of viruses to assess viral removal/inactivation of our downstream process for Snake Antivenom Immunoglobulin (SAI). Among the steps analyzed in the process, phenol addition was the most effective one, followed by heat, caprylic acid, and pepsin. The main steps are cited in sequential order (a) ammonium sulfate precipitation of immunoglobulins, (b) pepsin digestion to obtain F(ab'')2 fragments, (c) caprylic acid precipitation of nonimmunoglobulin proteins, (d) heat treatment, (e) ammonium sulfate precipitation of F(ab'')2 fragments, (f) tangential filtration, (g) ion-exchange chromatography, (h) tangential filtration, and (i) phenol addition. 34 We found no reports using both viruses as models for viral inactivation concerning the described purification steps. 52, 55 Phenol inactivated both viruses, which indicates that it might also be an effective preservative for human-derived immunoglobulins, when it comes to viral safety. cord-289093-si8btsab 2014 To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. The methodology in the previously published VACV screens varied considerably; Mercer et al [32] measured the growth of a thymidine-kinase-deficient VACV (strain Western Reserve) after only 8 h of infection, thereby identifying cellular proteins involved in the initial stages of virus replication but excluding analysis of viral spread. cord-291063-de7v4e5s 2009 The expressions of EBV-encoded miRNAs in clinical samples and computational analysis to predict putative targets were applied to unravel the biological functions of EBV miRNAs. These approaches showed that the miR-BARTs are abundantly expressed in latently infected epithelial cells, nasopharyngeal carcinomas, EBV-associated gastric carcinoma cell lines and tissues, Burkitt''s lymphomas latency type I, EBV positive primary effusion lymphomas, and diffuse large B-cell lymphomas, but at a significantly lower level in B cells. However, computational alignment of the potential HIV-1 miRNAs with specific human T-cell mRNAs identified potential cellular targets including genes encoding CD4, CD28 and interleukin-2, IL-3, and IL-12 [119] . The idea of targeting viral transcripts is not new, and RNA interference has been demonstrated to efficiently mediate inhibition of replication of human pathogenic viruses such as HIV-1, HCV, dengue virus, severe acute respiratory syndrome (SARS) coronavirus, poliovirus, human rhinovirus, influenza A virus, hepatitis D virus, HBV, HSV-1, HPV, JCV, EBV, and CMV in cell culture (reviewed in [12] ). cord-292335-al6v3b9x 2015 cord-292416-3hhi4wps 2020 Five years later, in 2020, when the World Health Organization declared the coronavirus disease 2019 (COVID-19)-caused by the newly emerging SARS-CoV-2 virus-to be a pandemic, this talk was widely acknowledged to be almost prophetic. 24, 25 All four reportedly mild pathogenic coronaviruses are associated with 10%-30% of cases of the common cold, 26 -28 yet they have the potential to cause severe lower respiratory tract infection in infants, in the elderly, and in patients with other underlying illness, 29 while hCoV-OC43, like SARS-CoV-2, has been associated with neurologic dysfunction as well. Development of animal models for SARS-CoV-2 infection is vital in providing comprehensive understanding of the pathogenic mechanisms involved but may also serve for screening anti-viral drugs and vaccines. Accordingly, transfusion of convalescent plasma is likely to be beneficial to SARS-CoV-2, 45 ,46 yet its effect on virus shedding and disease outcome must be evaluated when given to healthy individuals and patients at different stages and severity of the disease. cord-293038-pjjvfdnq 2008 We propose that this new structure, unique among enveloped viruses, assembles in association with the most stable component of Golgi stacks, the actin‐containing matrix scaffold, connecting viral replication and morphogenesis inside viral factories. Modified membranes harbouring viral replication complexes (RCs) frequently integrate into a complex structure known as the ''viral factory'' where the cytoskeleton participates, cell organelles are recruited and the different steps of the virus life cycle are sequentially connected. We propose that this new multifunctional structure associates with the actin-containing matrix of the Golgi stacks providing a stable scaffold for viral replication and early morphogenesis. LtA and CyD had very little or no effect, respectively, on viral replication and assembly as determined by measurement of infectious viral particles released to the culture supernatants at 6 and 10 h p.i. Complete tubes, virus budding profiles and viral particles assembled in Golgi stacks of cells treated with LtA, as observed in thin sections of treated cells studied by EM (not shown). cord-294478-3ickafd3 2008 cord-294592-zwvr57a0 2020 cord-297960-4x1j0iqg 2019 Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Global systems-level approaches including functional RNAi screens, interactome mapping technologies such as affinity-purification mass spectrometry (AP-MS), quantitative proteomics, and CRISPR/Cas9-based screens have provided unparalleled details and insights into the dynamics of host proteome in immune cells (21) (22) (23) (24) , host-virus interactome (15-17, 25, 26) , and also identified important host dependency factors of various viruses (25, 27, 28) . We hypothesized that combining a meta-analysis of host-virus protein-protein interactions of multiple viruses and functional RNAi screens would provide novel insights for developing broadspectrum antiviral strategies. High-Definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms cord-298019-gf2asni1 2014 While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. Peptides with a propensity for membrane binding can also interfere with enveloped virus entry by direct physical interaction with the hydrophobic surfaces present on cell membranes and/or fusion proteins. Since not all membranotropic peptides are able to cross the membrane bilayer, it is essential to identify structural characteristics of hydrophobic peptides know to enter the cell membrane to highlight any feature that is involved in the penetration which may help in the design of novel delivery tools. Dendrimer functionalization with a membrane-interacting domain of herpes simplex virus type 1: towards intracellular delivery cord-298033-kzdp9edn 2019 Quasispecies dynamics in disease prevention and control following statement will be obvious to the reader: "If a single mutation is able to confer resistance to an antiviral agent, and the mutation does not cause a significant selective disadvantage to the virus (fitness decrease) in the considered environment, a drug-resistant virus mutant will be present in most, if not all, virus populations" (Domingo, 1989) . The phenotypic barrier to drug resistance is equivalent to the fitness cost inflicted upon the virus by the mutations and corresponding amino acid substitution(s) required for resistance [Fitness cost is treated in Chapter 4 (Section 4.6) and in Chapter 7 (Section 7.4.2) in connection with the frequency of monoclonal antibody-or cytotoxic T-cell-escape mutants in viral populations]. For viruses that replicate in cell culture, it is possible to estimate the minimal viral population size needed to select a drug-resistant mutant which is generally positively correlated with the genetic barrier ( Fig. 8.5 ). cord-302111-kg0dmgq0 2020 Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Key Words: coronavirus; immunology; influenza virus; severe acute respiratory syndrome; viral pneumonia P neumonia is the leading infectious cause of hospitalization among adults and children in the United States (1) . Given the rapid spread of this virus and its association with severe pulmonary disease, the purpose of this review is to provide an overview of the presentation and immunology of viral pneumonia, principles of early management, and application to COVID-19. cord-303330-zh8wzza5 2020 cord-304424-048xo7jn 2018 That same year 36,789 colony sequences from DNase-treated RNA extracted from viral concentrates of human feces revealed a preponderance of pepper mild mottle virus and other plant viruses, but no new human viruses (Zhang et al., 2005) . While finding a new virus in the environment is not necessarily a problem in either DNA or RNA, the low fidelity of RNA polymerases and the sequence space they are capable of sampling, along with the possibility of recombination, lend themselves to new species and genera that are the trophies of metagenomic viral discovery. While metagenomics delivered on the promise of finding novel human viruses, viral discovery in humans has increasingly become a tragic story of patients interacting with the wrong squirrel or tick on the wrong day and most samples sequenced are frankly negative (Hoffmann et al., 2015; McMullan et al., 2012) . The greatest paradigm shifter in recent viral metagenomics work has been the sheer number and diversity of novel RNA viruses present in arthropods and invertebrates. cord-305195-e41yfo89 2016 cord-306424-gf0bglm0 2017 cord-306921-3afgpunj 2019 A small siRNA screen targeting human membrane trafficking genes identified vasolin-containing protein (VCP-p97) as an important protein essential after PV viral replication and it interacts and colocalizes with 2 BC/2C as well as 3AB/3B in poliovirus infected cells [83] . Human host factors-viral protein studies identified nuclear factor; adenosine-uridine (AU)-rich element RNA binding factor 1 (AUF1) is targeted for cleavage by CV-B3 viral 3C protease upon translocation to the cytoplasm for enhanced stability of the IRES dependent viral RNA production [112] , similar antiviral observations were made for poliovirus, coxsackievirus and human rhinovirus [113] . A subsequent study by Mohamud and colleagues demonstrated that SQSTM1 and another host factor calcium binding and coiled-coil domain-containing protein 2/nuclear dot 10 protein 52 (CALCOCO2) regulate CV-B3 virus infection by targeting autophagy receptors; via their interaction with viral protein 1 [177] . cord-307354-dkwcheu0 2015 Alpha-herpesviruses such as herpes simplex-1 (HSV-1) express a FEN1-like nuclease termed virion host shutoff protein (vhs) that is directed to mRNAs through interactions with the translation Fig. 1 . Quality control decay pathways such as NMD recognize aberrant mRNAs during translation, including the presence of premature termination codons (PTC), and induce endonucleolytic cleavage, whereupon the fragments are degraded by exonucleases. The RNAi pathway restricts gene expression by processing the long double stranded RNAs frequently generated during viral replication into short interfering RNAs (siR-NAs), which guide endonucleolytic cleavage of complementary target mRNAs. Although mammalian cells possess the RNAi machinery, in most cases RNAi does not appear to play a significant antiviral role, and has instead been supplanted by the protein-based interferon response (Cullen, 2014) . Small interfering RNAs that deplete the cellular translation factor eIF4H impede mRNA degradation by the virion host shutoff protein of herpes simplex virus cord-307813-elom30nx 2018 cord-307817-2vy28i4m 2014 cord-308126-wpxhk0pf 2020 cord-309642-wwaa6ls0 1986 7 · 18 · 84 · 133 Such restrictions function at the cellular level either as the presence or absence of appropriate cell surface receptors (in some instances, they have been shown to be inherited as dominant alleles in a Mendelian manner) 9 · 18 · 26 · 46 · 68 · 97 ·u 9 · 120 or the intracellular hospitality of the cell (several genetic host restrictions on virus replication have been identified).18·32·59·80·82·108·109·120·126 Restricted growth of several DNA viruses in some cells results in transformation without production of progeny viruses. 112 The phenomenon appears to be mediated by virus-induced receptors on the surface membrane of cells and may be one mechanism of the often-encountered secondary bacterial infections associated with viral diseases. 51 · 52 · 104 Viral respiratory tract disease is a consequence of mechanical and biochemical injury to epithelial cells and alveolar macrophages, which can, in the most severe instances, result in secondary bacterial infection, pneumonia, and death. cord-310920-itqwhi6a 2020 cord-312332-rwmuucsp 2020 cord-314024-n6l2804j 2020 We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer 39 viral growth parameters and predict the effects of antiviral treatments. We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer 39 viral growth parameters and predict the effects of antiviral treatments. We 162 considered a simple case where the drug effectiveness is assumed to be constant after therapy 163 initiation (see methods) and we calculated the minimal efficacy that would be needed to 164 generate more than 2 logs of viral decline at peak viral load in the 13 studied patients (Fig. 1) . For a putative 167 treatment initiated at the time of infection, symptom onset, or 3 days post symptom onset, a 168 median efficacy of at least 60, 90 and 99% in reducing viral replication would be needed, 169 respectively, to generate more than 2 log of decline in the peak viral load (Fig. 1) . cord-314560-rswa5zdn 2006 RNA interference (RNAi), initially recognized as a natural antiviral mechanism in plants, has rapidly emerged as an invaluable tool to suppress gene expression in a sequence-specific manner in all organisms, including mammals. However, in recent years, a new type of genomic immunity mediated by RNA interference (RNAi) has emerged and has sparked intense interest as a potential treatment strategy for a variety of diseases, including viral infections, cancer and degenerative diseases [1] [2] [3] [4] . In RNAi, long double-stranded (ds) RNA generated during viral infection is cleaved by an enzyme termed Dicer into short, 21-23 nucleotide (nt) dsRNA molecules termed small interfering (si)RNAs that mediate sequence-specific gene silencing [5, 6] . A landmark development in the field occurred with the discovery that the introduction of 21-nt-long synthetic RNA resembling the Dicer-processed siRNA into mammalian cells induces sequence-specific gene silencing without evoking the interferon response [10] . cord-315130-8g2ih8zl 2020 cord-317037-1qydcc5e 2020 cord-317277-rr9zue4l 2020 Cell-free viral particles can be released into the extracellular space through different mechanisms, such as: (a) cell lysis induced by viral proteins, as is the case for many non-enveloped viruses such as reoviruses, rotaviruses, adenoviruses and picornaviruses (Giorda and Hebert, 2013; Hu et al., 2012; Nieva et al., 2012) ; (b) by budding directly from the plasma membrane, where virions acquire their envelope, as is the case of human immunodeficiency virus (HIV-1), influenza, paramyxoviruses, and pneumoviruses (Lorizate and Krausslich, 2011; Votteler and Sundquist, 2013; Weissenhorn et al., 2013) ; (c) by exocytosis of intracellularly assembled viral particles, as is the case for bunyaviruses, flaviviruses and coronaviruses (Cifuentes-Munoz et al., 2014; Lorizate and Krausslich, 2011) . An interesting observation made for alphaviruses is that the filopodia-like extensions are not able to transfer cytosolic or plasma membrane components, suggesting they are not openended connections like TNTs. Instead, viral particles are hypothesized to bud into a protected space at the filopodial tip and then rapidly enter the target cell, preventing access of neutralizing antibodies. cord-318495-1w74wf02 2019 cord-318749-k91oku7h 2020 Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Similarly, ribosomes are required for the protein synthesis of host cells and viruses, but the biogenesis factor RBFs can also impact the proliferation of virus and cell-intrinsic immune responses. The multifunctional nucleolar phosphoprotein nucleophosmin (NPM) plays a lead role in ribosome biogenesis to stimulate RNA Pol I-dependent transcription (Li and Hann 2013) and regulates SARS-CoV, IBV, HIV-1, HCV Recruited by viral proteins to facilitate viral replication Chen et al. RPS25 deletion in yeast or mammalian cells has minimal effects on cellular protein synthesis, which implies that this ribosomal protein may be selectively required for viral IRES-mediated translation (Jack et al. Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication cord-318751-4v2tl0gi 2013 cord-318853-mxyxwkhx 2005 cord-319215-8tdtia5w 2010 cord-319675-mwy3t1ny 2016 cord-319761-bu5pzbnv 2005 Accordingly, this review focuses on specific viral cell interactions that allow the virus to survive the cellular attack and evade the immune system, establish persistent infections, and cause chronic disease. 13, 14 Viruses regulate apoptosis by several mechanisms including the targeting of the tumor suppressor gene product p53, the Fas death receptor, and by producing caspase inhibitors and viral Bcl-2 homologs. 24, 25 The alpha herpesvirus HSV-1 encodes several antiapoptotic gene products (ie, ICP4, ICP27, c34.5, U s 3, gJ) [26] [27] [28] [29] [30] that modulate apoptosis at several levels, including antagonism of double-stranded RNA-activated protein kinase (PKR), a downstream induction molecule of the interferon signaling pathway 31, 32 Of note, all c-herpesviruses express viral homologues of cellular antiapoptotic genes, including 1 or 2 Bcl-2 homologues. In the majority of infections, viruses encode products that antagonize either the IFN signal transduction pathway or cellular proteins induced by IFN that are responsible for inhibiting virus replication (Fig 2) . cord-320015-lbr2q4qh 2011 cord-320713-b37c8aye 2009 6 The rate of translation initiation in mammalian cells is also controlled by sequence elements within the 5 0 -and 3 0 -UTRs of mRNAs which regulate this process by providing sites for interaction of regulatory proteins and RNAs. These include upstream open reading frames (uORFs), microRNA (miRNA) target sites, and polyadenylation elements. 5 It was suggested that alternative eIF4F complexes lacking PABP could selectively promote the synthesis of viral, but not host, proteins, so that KSHV-encoded mRNAs would compete more effectively for host translation machinery in infected cells. Picornavirus translation is directed by internal ribosome entry sites (IRESs) within the 5 0 -UTRs of the viral RNAs. The central one-third of eIF4G, containing the eIF3 and one eIF4A-binding domain, is sufficient to support translation initiation from these IRESs. 43 This allows picornavirus RNAs to compete effectively for the host translation machinery following infection, although the situation appears to be more complicated than this (see Section III). cord-323404-3mw4q7m3 2003 cord-325230-3kg4oe4g 2010 cord-325626-r7k7u7ro 2020 cord-325750-x7jpsnxg 2012 In this article, we review virus discovery techniques with a focus on metagenomic approaches that employ high-throughput sequencing technologies to characterize novel viruses. This method lacks sufficient sensitivity to detect viruses when the viral burden is low or when the DNA sequence of the suspected etiological agent is not clearly distinguishable from the control sample [31] . The following items should be included in any report on viral metagenomic studies: firstly, the sequencing platform and its version number; secondly, raw sequence data accession numbers in a public database; thirdly, details about the bioinformatic analysis, including the homology search tool and the database being used to assign the taxonomy, and their versions; fourthly, a list of known and previously unknown viruses found, clearly showing if the ''novel'' viruses are new strains of a previously described species or completely different viruses; and fifthly, causality evidence if any. cord-326273-6rp12py3 2004 cord-327444-y2464gjh 2014 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-329162-6w8qcv1c 2018 The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have applied this approach to design genus-specific primer pairs for targeted enrichment of cDNA from zoonotic RNA viruses and have evaluated it using several samples from birds. The control samples cDNA was obtained by reverse transcription reaction performed on 5 L of the extracted RNA using the Reverta-L RT kit (AmpliSens; total volume of the reaction mixture is 20 L); after that 5 L of the reaction mixture containing cDNAs was further used for evaluation of the ability of the primer pair to amplify the targeted region of viruses, both in single and in multiplex PCR format. cord-329306-p5wmqmvj 2014 Rhinovirus infection is typically associated with the common cold and has rarely been reported as a cause of severe pneumonia in immunocompetent adults. Rhinovirus infection can extend to lower respiratory tract in children [4] [5] [6] or immunocompromised hosts 7, 8 , but is generally not concerned as singular cause of severe pneumonia, especially in immunocompetent adults. Although technical advances have allowed for increased detection of viral pneumonia, viral infections other than influenza are generally not considered as causes of severe respiratory tract infection in immunocompetent hosts, because viral clearance usually occurs rapidly in healthy individuals. Therefore, it is still believed that severe viral pneumonia caused by frequently exposed rhinovirus could hardly occurs in immunocompetent adults. On the contrary, our relatively young immunocompetent patient suffered severe rhinovirus pneumonia without bacterial co-infection, which was confirmed by BAL fluid analysis, and not by the nasopharyngeal specimen. Rhinovirus associated with severe lower respiratory tract infections in children cord-329710-vqorb6j7 2020 We highlight past and recent findings in essential coronavirus proteins, including RNA polymerase machinery, proteases, and fusion proteins, that offer opportunities for the design of novel inhibitors of SARS-CoV-2 infection. Many recent scientific reviews and essays have outlined vaccine efforts, as well as viral and host targets that are the focus of current campaigns aimed at redirecting clinically used compounds for COVID-19. The FDA-approved COVID-19 drug, remdesivir, is a nucleotide analog originally developed to treat Ebola infections (caused by another single-stranded RNA virus) and recently shown to inhibit the SARS-CoV-2 RdRP. HIV protease inhibitors lopinavir and ritonavir, included in the SOLIDARITY trial despite mixed reviews in the clinic, have been predicted to bind SARS-CoV-1 and CoV-2 3CL pro (96% sequence identity) based on computational studies. Using a recently solved crystal structure of the HR1 and HR2 domains of the SARS-CoV-2 S protein, lipidated peptide fusion inhibitors have been designed that inhibit pseudovirus infection of cells with IC 50 values in the single-digit nanomolar range. cord-330200-l6bnxi40 2020 title: Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. Only two articles report dynamics of SARS-CoV-2 viral RNA and antibodies with serial samples, but the observation periods are within 30 days. In this study, we investigated the profiles of viral RNA, IgM, and IgG in a group of patients with confirmed SARS-CoV-2 pneumonia over an 8-week period after symptom onset. Demographic data, symptom onset time, clinical features, radiological findings, routine laboratory results, and the results of SARS-CoV-2 viral RNA in throat swabs, sputum, and stool samples were recorded during hospitalization and follow-up. We investigated the serial viral load and dynamics of antibodies from patients infected with SARS-CoV-2 over an eight-week period following the onset of symptoms. cord-330684-3hxau5vt 2012 Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Based on the well-described case of AMDV, we can In some cases, apoptosis induction by the host cell leads to exactly what is expected, namely viral attenuation, but surprisingly with the help of viral protein cleavages. However H-1PV is able to activate caspases in non-transformed cells, leading to the cleavage of NS1, a non-structural protein (NS) notably involved in viral DNA replication and gene expression by transactivating P38 promoter, which controls the synthesis of capsid proteins. In HRT18jap1 cells, the infection causes apoptosis but is not productive, suggesting that caspase activation (and possibly N caspase cleavage) prevents progeny virion generation. Induction of caspase activation and cleavage of the viral nucleocapsid protein in different cell types during Crimean-Congo hemorrhagic fever virus infection cord-331673-xv1tcugl 2020 For instance, in the case of Herpesviridae and Paramyxoviridae viruses (both enveloped viruses with embedded viral-encoded glycoproteins), AgNPs can effectively reduce their infectivity, by blocking the interaction between the viral particles and the host cells with an antiviral activity strictly dependent on the size and ζ potential of the AgNPs. As a general observation, it was reported that smaller nanoparticles have better antiviral effect. cAgNPs could reduce cytopathic effects induced by RSV and showed efficient antiviral activity against infection by directly inactivating the virus prior to entry into the host cells. have reported that porous AuNPs are able to inhibit influenza A infection more efficiently than nonporous AuNPs. 39 This effect has been associated with the higher surface area of the porous material that favors their interaction with capsids and thus increases their antiviral activity ( Figure 4 ). cord-332632-u2ud0vmq 2016 In particular, the unique extension of ''self'' to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host''s own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Thus, the survival strategy of BVDV consists of being non-cytopathogenic and producing less dsRNA than its cp counterpart, and expressing the IFN antagonists N pro as the first protein in order to reduce or even avoid IFN production in infected cells and E rns to degrade immunostimulatory viral RNA before they might activate the host''s PRRs. Notably, both pestiviral IFN antagonists are not only required to constantly maintain innate immunotolerance during persistent infections, but they also play an important role in acute infections [25] . cord-334010-gxu0refq 2016 The sema-domain is the [18, 43] Fusion with host cell membrane Sialic Acid and attachment [43] 3-5 million cases Worldwide [78, 105] SARS-CoV Spike(S) glycoprotein [25, 115] Membrane fusion [115] 8422 within the duration of 1st November 2002 to 7th August 2003 occurring worldwide [113, 114] Hepatitis C virus E1 and E2 [55, 98] Binding to Host receptor and Conformational change necessary for membrane fusion [98] 130 to 150 million people globally [103, 106] Human immunodeficiency virus 1 gp120, gp160, gp41 [16] Intracellular transport [16] 35 million globally up to 2013 [83, 104, 108, 112] Zaire Ebola virus Spike Protein Gp1-Gp2 [64] Primary Host cell activation [64] up to 28th June 2015 total 27,550 cases [107, 110, 111] Dengue virus E (dimer) [64] Host cell fusion and attachment [64] WHO reported recently that there are 390 million dengue infections per year globally [109] . cord-334127-wjf8t8vp 2015 This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. Whereas primary databases are archival repositories of sequence data, reference databases provide curated datasets that enable a number of activities, among them are transfer annotation to related genomes (11) (12) (13) , sequence assembly and virus discovery (14) (15) (16) (17) , viral dynamics and evolution (18) (19) (20) and pathogen detection (14, (21) (22) (23) . The second model captures and standardizes host information for all viruses, and whenever a new RefSeq record is created, a manually curated ''viral host'' property is assigned to the relevant species within the NCBI Taxonomy database. The link to the Retrovirus Resource (http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses) provides access to the Retrovirus Genotyping Tool and HIV-1, Human Interaction Database (50, 51) . cord-337361-salby0fu 2013 In some viruses, the frequency of homologous crossing-over is very high and practically every replicated viral RNA molecule can be considered as chimerical in nature, as we have demonstrated for brome mosaic virus (BMV) RNAs (Urbanowicz et al., 2005) . The generally accepted mechanism of RNA recombination is currently explained by a copy-choice model where the viral RNA polymerase (RdRp) complex in mRNA viruses [reverse transcriptase (RT) in retroviruses] changes templates during synthesis of the nascent strand (Galetto et al., 2006) . Among the factors known to promote replicase to switch are sequence homologies between recombination substrates along with secondary structures at the crossover sites, as demonstrated with the BMV and other systems (Figlerowicz and Bujarski, 1998; Nagy et al., 1999b) . Comparison among three plant RNA virus replication systems (TBSV, BMV, and dianthoviruses) reveals general patterns within the stepwise process of viral replicase complex assembly which requires concerted involvement of protein-protein, RNA-protein, and protein-lipid interactions (Mine and Okuno, 2012) . cord-337636-3yc0ribg 2020 Herein, we have developed a method to detect virus off swabs using solely shaker-mill based mechanical lysis and the transfer of the viral lysate directly to a PCR assay for virus detection, bypassing the substantial reagent and time investments required for extraction and purification steps. Swabs were spiked in serial dilutions from 1.2 × 10(6) to 1.2 × 10(1) copies/mL and then placed in 2 mL tubes with viral transport media (VTM) to mimic the specimen collection procedures in the clinic prior to processing via shaker-mill homogenization. RESULTS: HCoV-229E in vitro spiked swabs were processed in a novel two-step, direct-to-PCR methodology for viral detection. CONCLUSION: We have proven that the shaker-mill homogenization-based two-step, direct-to-PCR procedures provides sufficient viral lysis off swabs, where the resulting lysate can be used directly in PCR for the detection of HCoV-229E. Using human coronavirus 229E (HCoV-229E) as our model organism, we developed a novel two-step methodology of optimized shaker-mill homogenization parameters that allowed for direct-to-PCR viral detection. cord-337673-1nau263l 2006 Recently, small interfering RNA (siRNA) has shown promise in the protection from viral invasion, as it can inhibit the expression of viral antigens and accessory genes as well as control the transcription and replication of the viral genome. Genes encoding vital proteins in reproducing SARS-CoV virions can be chosen for chemotherapeutic intervention (e.g., those coding for S, 3C-like protease [3CLpro], RNA-dependent RNA polymerase and possibly other gene products involved in viral-protein-mediated processes) [81] first demonstrated that siRNA was able to silence the replicase of SARS-CoV (1a region of the genome) and that this approach was effective in vitro against SARS-CoV. [82] subsequently observed that vector-based siRNAs could inhibit the replication of SARS-CoV, and showed that expression in the plasmid, pSUPER, of siRNAs specifically targeting viral RNA polymerases could block the cytopathic effects of SARS-CoV on Vero cells. [86] showed that three chemically synthesised siRNA duplexes targeting viral RNA polymerases, and one targeting the S gene potently inhibited SARS-CoV infection and replication in fetal rhesus kidney cells (FRhK-4) . cord-338083-77re4l0w 2005 The genetic diversity that occurs among isolates of BVDV is characteristic of RNA viruses that exist in nature as quasispecies (a swarm of viral mutants). However, altered base sequence in this region of the viral genome has been identified after passage of the virus in cell culture, and has been detected in viral RNA that was extracted from tissues of an infected animal [20, 21] . The selection of the antigenic variants likely occurred during the acute infection of the dams of those PI cattle and resulted in transplacental transmission of slightly different BVDV to a group of fetuses. Genetic and antigenic variability in bovine viral diarrhea virus (BVDV) isolates from Belgium Pathogenesis of primary respiratory disease induced by isolates from a new genetic cluster of bovine viral diarrhea virus type I Clinical and immunologic responses of vaccinated and unvaccinated calves to infection with a virulent type-II isolate of bovine viral diarrhea virus cord-338804-nreqluol 2014 Viral interactions with these receptors can have a significant impact upon several aspects of viral pathogenesis, including determining the cell or tissue tropism of a virus or even whether a virus can efficiently infect and cause disease in a specific host species. Therefore, viruses that are defective in their ability to antagonize the host type I interferon system are often unable to replicate and spread efficiently within the host, illustrating the importance of viral immune evasion strategies in determining whether a virus will be pathogenic ( Figure 2) . (b) If the virus effectively interferes with the type I interferon response, interferon will be prevented from inducing a robust antiviral state within the host, and the virus is able to replicate to higher levels, will spread more efficiently, and may cause more severe disease. Therefore, like other aspects of viral pathogenesis, a complex series of virus-host interactions determines whether infection with cancer associated viruses ultimately results in disease development. cord-339288-y8woqsii 2016 Self-replicating RNA derived from the genomes of positive strand RNA viruses represents a powerful tool for both molecular studies on virus biology and approaches to novel safe and effective vaccines. Three years later, the performance of poliovirus cDNA clones could be significantly ameliorated through the introduction of SV40 transcription and replication signals and transfection of the resulting construct into cells expressing the SV40 large T antigen [14] , thus ensuring replication of the DNA-plasmid in eukaryotic cells leading to a higher yield of viral RNA and recovered virus (Fig. 2, left part) . The resulting virus CP7_E2alf was only able to infect pigs and thus displayed the Fig. 3 Generation of a chimeric viral genome from two parental RNAs. On the level of a cDNA construct, one protein-coding sequence is replaced by the corresponding gene of the other virus (principle used for the pestivirus vaccine CP7_E2alf [58] ). cord-340423-f8ab7413 2016 We then discuss evidence that at least some RNA viruses have a replication fidelity that is poised to maximize genome sequence space without incurring catastrophic lethal mutations and describe how this can be exploited to control viral infections. The error-prone nature of polymerase activity, coupled with the absence of a proofreading mechanism, is the key reason why RNA virus genomes acquire mutations and exist as a swarm of genetic variants. The mutation rate of the viral polymerase, coupled with the replication mode that the virus employs (and extrinsic factors, described in the following text) will determine the extent of genetic variability of viruses released from an infected cell. Thus, it is possible that the high mutation rates of RNA viruses are simply a consequence of polymerases that are under selective pressure to replicate genomes very rapidly to ensure efficient viral infection [79] [80] [81] . cord-342133-khrljehj 2015 To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). To evaluate the circulation of the different hBoV types and the possible relationships between viral load, virus genetic characteristics, and the severity of infection, nasopharyngeal swabs were collected from otherwise healthy children attending the emergency room of the Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Italy, due to a respiratory tract infection arising between November 1 and March 31 during 3 winters (2009-2010, 2011-2012, and 2013-2014) . Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children cord-342660-xigv4u3f 2020 We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. We thus conducted a retrospective cohort study in kidney transplant recipients (KTR) in Alsace, Grand-Est France, to determine the dynamics of nasopharyngeal and plasma viral loads and SARS-CoV-2 serology and to study their association with mortality and severe forms of COVID-19. . https://doi.org/10.1101/2020.06.17.20132076 doi: medRxiv preprint positive viral load greater than 3 log10 copies/reaction after D10, and ten patients (24.4 %) In this retrospective study conducted in a sample of 40 immunocompromised KTR hospitalized for COVID-19, we precisely determined the temporal evolution of nasopharyngeal and plasma SARS-CoV-2 loads, as well as the serological response to the virus. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China cord-343377-6muareue 2016 Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Bennett et al performed a surveillance study of viral respiratory infections in two NICUs. All infants of a gestational age < 33 weeks were tested twice a week using multiplex RT-PCR ELISA. Detection of respiratory viral infections in neonates treated for suspicion of nosocomial bacterial sepsis: a feasibility study Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study Unrecognized viral respiratory tract infections in premature infants during their birth hospitalization: a prospective surveillance study in two neonatal intensive care units Viral respiratory tract infections in the Neonatal Intensive Care Unit cord-343470-w215pzdc 2020 Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. First, the viral protein VP16, which is packaged into the tegument layer of incoming virions, recruits host proteins, including host-cell factor 1 (HCF-1) and octamer-binding factor (Oct-1), in order to form a complex that recruits the histone demethylases lysine-specific demethylase 1 (LSD1) and Jumonji domain 2 (JMJD2) family members as a means to remove repressive H3K9 marks from viral immediate early promoters 42 Upon entry into the cell nucleus, the DNA of many viruses initiates the replication process adjacent to subnuclear structures called pro-myelocytic leukaemia nuclear bodies (PML-NBs). cord-345168-3w32v2fm 2009 Comparison was made between patients with pandemic H1N1 virus and seasonal influenza virus infection regarding their demographics, underlying diseases, presenting symptoms, total white blood cell counts, absolute lymphocyte counts, and initial pre-treatment viral load in respiratory specimens on the day of diagnosis. Among patients with pandemic H1N1 virus infection, the same parameters was compared between those with longer duration (!5 days) and shorter duration ( 4 days) of viral shedding, as defined by the time from onset of symptoms to the last positive sample by RT-PCR. For both pandemic H1N1 cases and seasonal influenza historical controls, respiratory specimens collected on the day of onset of symptoms (day 0) had the highest mean viral load (Fig. 1 ). For patients who presented to hospital between days 0 and 3 after onset of symptoms, the initial pre-treatment viral load in pandemic H1N1 cases was lower than the seasonal influenza historical controls. cord-346290-my8ow5ee 2020 Respiratory viruses are responsible for a variety of clinical syndromes including the common cold, acute otitis media, laryngitis, sinusitis, pneumonia, bronchiolitis, influenza-like illness, and exacerbations of asthma and chronic obstructive pulmonary disease. Treatment modalities include over-the-counter and non-specific remedies along with a small number of specific antiviral medications such as the influenza neuraminidase inhibitors or palivizumab against respiratory syncytial virus. Viruses of the family of Pneumoviridae form enveloped, spherical or filamentous virions with 100-200 nm in diameter, which contain a single, linear, negative-sense RNA genome. Human bocavirus 1 (HBoV1), a member of the species Primate bocaparvovirus 1, in the genus Bocaparvovirus and the subfamily of Parvovirinae, is strongly associated with upper and lower respiratory tract infections in young children. The common cold is a rather benign clinical entity, which may however be complicated by secondary bacterial infections, otitis media, sinusitis, pneumonia, and asthma exacerbations; severe courses of disease and death may occur in young children and immunocompromised patients. cord-346916-jj4l9ydl 2020 Moreover, despite the molecular mimicry set by RNA viruses to resemble cellular mRNAs and escape host recognition, the viral nucleic acid still needs to embark on a long journey through a hostile cell environment and must overcome the obstacles put in place by the host antiviral system in order to be translated and replicated. Another example, is the zinc-finger antiviral protein (ZAP), which binds vRNAs containing a ZAP response element (ZRE) and induces RNA degradation via interaction of its N-terminal domain with host decay machinery mediated [75] (Fig. 1 ). In fact, IRES elements present in the genome of different families of RNA viruses lack overall conserved features [146, 147] .The classification of viral IRESs in four types stems from their structural organization, their respective dependence on sets of translation initiation factors, and whether they use scanning or instead directly recruit ribosomes to the start codon [148] (Fig. 2) . cord-347731-eqxn6auk 2020 The data sources included were (i) longitudinal clinical, pharmacokinetic (PK), and virologic data from patients with severe acute respiratory syndrome‐2 (SARS‐CoV‐2) infection who received HCQ with or without azithromycin (n = 116), (ii) in vitro viral replication data and SARS‐CoV‐2 viral load inhibition by HCQ, (iii) a population PK model of HCQ, and (iv) a model relating chloroquine PKs to corrected QT (QTc) prolongation. 12 The drug effect over time on viral replication rate was established by simulating unbound plasma concentrations or unbound lung tissue concentrations using a previously defined partition coefficient (10 2.45 ; HCQ unbound fraction assumed to be ~ 50%) and using the established in vitro sigmoidal efficacy parameters. 3, 9, 10 Viral kinetics were estimated from in vitro replication rate of severe acute respiratory syndrome-coronavirus (SARS-CoV)-1 and unbound drug concentration in plasma and lungs were simulated with HCQ PK model. cord-349358-leicos9j 2006 During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Likewise, expression vectors of siRNAs specific for two different regions of the WNV genome protected 293T cells from WNV infection, and significantly reduced viral RNA replication and virus production [35] . From the reports on the use of siRNA against human viral pathogens causing acute disease, we could learn that for each specific pathogen infecting a specific cell lineage or tissue, we would probably need to perform an indepth assessment, with proper in vitro and in vivo models, and develop specific delivery systems. The most challenging part of RNAi approaches for chronic viral infections is to design the best delivery method that would facilitate the targeting of the specific organ/cells with the appropriate expression system, for durable intracellular levels of gene-silencing effect. cord-353297-jizitnfl 2008 The requirements for an ideal biological warfare agent include availability, ease of production, stability after production, a susceptible population, absence of specific treatment, ability to incapacitate or kill the host, appropriate particle size in aerosol so that the virus can be carried long distances by prevailing winds and inhaled deeply into the lungs of unsuspecting victims, ability to be disseminated via food or water, and the availability of a vaccine to protect certain groups. Instead, the ectromelia virus vector expressing IL-4 altered the host''s immune response to this virus resulting in lethal infections in normally genetically Classification of viral agents that are considered to be of concern for bioterrorism and biowarfare and those that have been weaponized or studied for offensive or defensive purposes as part of former or current national biological weapons programs resistant mice (e.g., C57BL/6). cord-353554-98uzivsk 2018 title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. 64 The virus-receptor interaction was reported to be a principal determinant of viral host 65 range, tissue tropism and cross-species infection [11, 16, 22] . However, we found the viral receptor tended not to interact with each 248 other ( Figure S3D 270 Since the virus has to compete with other proteins for binding to the receptor, proteins (Table S5) . 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-353810-mf753ae9 2019 This report also describes a successful application of capture-based purification as a direct RNA sequencing strategy that addresses certain limitations of current strategies in sequencing RNA viral genomes. Based on the mapping rates to human and DENV1 reference genomes for pre and post-capture groups, shown in Table 2 , purification factor was calculated to be 272-fold. The minimum coverage required for variant calling was, as described above, benchmarked to that of Illumina reads so that the effectiveness of our capture-based purification method could be more accurately evaluated based on the higher error read rates of direct RNA sequencing technology. Indeed, after comparison of the postcapture and concentrated post-capture sequencing runs (Table 2) , the 2.5-fold increase in the percentage of reads mapping to DENV1 suggests that scaling our method greatly improved the signal-to-noise ratio of this particular downstream RNA assay. cord-355872-z6vsjmxn 2019 Characterization of bacterial and viral relationships in mosquito arthropods demonstrated a symbiotic relationship between the bacterium and host, limiting dengue virus infection and potentially revealing new antiviral strategies [39, 40] . The Ebola virus outbreak in West Africa resulted in 26,648 cases and 11,017 documented deaths, and genomic sequencing was applied in near real-time to provide information to aid in containing the outbreak [44, 45] . During the Ebola virus outbreak, sequence analysis of the viral genome over time demonstrated changes which could make the pathogen resistant to therapeutics such as siRNAs, phosphorodiamidate morpholino oligomers (PMOs), and antibodies [56] . This agnostic method is appropriate for identifying changes in the human transcriptome as a result of an emerging viral infection to show specific mechanisms of immune response evasion and other effects in the host''s biology at the transcriptomic level. cord-355913-fhvt1ht1 2016 Little is known about what determines whether a given picornavirus positive-sense RNA molecule will be directed (1) to a replication complex (a structure bound to smooth endoplasmic reticulum), where it serves as template for transcription by RNA-dependent RNA polymerase into negative-sense RNA, or (2) to a ribosome, where it serves as mRNA for translation into protein, or (3) to a procapsid, with which it associates to form a virion. In the case of positive-sense single-stranded RNA viruses, the incoming RNA genome can bind directly to ribosomes and be translated in full or in part without the need for any prior transcription; all other forms of incoming viral RNA must first be transcribed to produce mRNA, in order to begin the process of expression of the infecting viral genome.