# ent

id: cord-003676-kr4o8hoc
type: PROTEIN
entity:
  PRV3M S4 F 5 CAT TGT CAC TCC GAT TAT GG 3 PRV3M S4 R 5 TGG GAG GGT GCA GAG CAT AG 3 PRV3M S4 probe5 56 FAM GTA GGC ATG CCG CTC GTG GAA TCC A 3BHQ_1 3


id: cord-003676-kr4o8hoc
type: ORG
entity:
  the SingHealth Institutional Animal Care and Use Committee of the SingHealth Experimental Medicine Centre


id: cord-266987-ikt8r2o1
type: DISEASE
entity:
  coronavirus 2019 nCoV lab lab biosafetyguidelines html Accessed 21 March 2020 Isolation of HCoVs in cell culture


id: cord-003573-ekxq4l9a
type: ORG
entity:
  the Committee on the Ethics of Animal Experiments of the Wuhan Institute of Virology Chinese Academy of Sciences


id: cord-288741-69pgy833
type: DNA
entity:
  forward primer F CATAGAAGATTCTAGACACCATGGATTACA AGGACGACGATGACAAGgccaagggattctacatttc R ATTTAAATTCGAATTCttagctgtgctctatgaacca


id: cord-297942-6wdwrttn
type: ORG
entity:
  Peking Union Medical College Hospital V2 0 Working Group of 2019 Novel Coronavirus Peking Union Medical College Hospital


id: cord-297942-6wdwrttn
type: ORG
entity:
  Department of Infectious Diseases Peking Union Medical College Hospital Department of Infectious Diseases Peking Union Medical College Hospital Department of Internal Medicine ICU Peking Union Medical College Hospital Hongwei Fan Department of Infectious Diseases


id: cord-318392-r9bbomvk
type: DNA
entity:
  ORF1a n 28 ORF1b n 19 32 kDa non structural protein NSP gene n 6 hemagglutinin esterase HE gene n 2 S gene n 18 4 9 kDa NSP gene n 2 4 8 kDa NSP gene


id: cord-318392-r9bbomvk
type: ORG
entity:
  the International Committee on Taxonomy of Viruses International Union of Microbiological Societies Virology Division Comparative


id: cord-329555-y3cp5wza
type: WORK_OF_ART
entity:
  Weatherall Report NIH Guide for the Care and Use of Laboratory Animals USDA Animal Welfare Act Institute for Laboratory Animal Research Guide


id: cord-329555-y3cp5wza
type: ORG
entity:
  the Uganda National Council for Science and Technology and Makerere University Biological Field Station


id: cord-291076-p350i54m
type: DISEASE
entity:
  influenza A virus H1N1 4 H5N1 5 H7N9 6 severe acute respiratory syndrome coronavirus SARS Cov 7 Middle East respiratory syndrome coronavirus MERS


id: cord-291076-p350i54m
type: DISEASE
entity:
  influenza A H5N1 Role of host cytokine responses in the pathogenesis of avian H5N1 influenza viruses


id: cord-326512-iex98lr1
type: PROTEIN
entity:
  anti human CD20 FITC Invitrogen Carlsbad CA IgG APC H7 CD3 Pacific Blue CD27 PerCP Cy5 5 BD Biosciences Franklin Lakes NJ


id: cord-282140-teplpmi6
type: DISEASE
entity:
  influenza A virus and 35 of all samples collected Sequence analysis of full length haemagglutinin HA


id: cord-282140-teplpmi6
type: DISEASE
entity:
  influenza A H5N1 clade 1 1 2 reassortant viruses A Cambodia X0121311 2013 and A Cambodia X0125302 2013 which were isolated from human cases during 2013 and influenza A H9N2 virus A


id: cord-282140-teplpmi6
type: DISEASE
entity:
  influenza A H5N1 viruses detected during the study Supplementary Figure S1 For other viruses full gene sequences could not be generated for all fragments Supplementary Table S1 All A H5N1 viruses detected in the study clustered with the clade 1 1 2 reassortant strains associated with human cases and poultry outbreaks of A H5N1 during 2013 10 Non H5 avian influenza detection A large number


id: cord-282140-teplpmi6
type: DISEASE
entity:
  influenza A H5N1 virus Influenza Other Respir A high diversity of Eurasian lineage low pathogenicity avian influenza A viruses


id: cord-354790-xx6imhzb
type: DISEASE
entity:
  human immunodeficiency virus HIV hepatitis B virus HBV hepatitis C virus HCV influenza virus dengue virus Ebola virus


id: cord-314254-9ye8tfvz
type: CELL_LINE
entity:
  domestic horses United kingdom A novel hepacivirus with an unusually long and intrinsically disordered


id: cord-315355-a25ba7dz
type: DNA
entity:
  bottom ORF open reading frame S spike E envelope M membrane N nucleocapsid NS6 NS7a NS7b and NS7c represent nonstructural proteins 6 7a 7b and 7c respectively c Phylogeny


id: cord-315355-a25ba7dz
type: CHEMICAL
entity:
  gammacoronavirus and deltacoronavirus Full length genome sequence of porcine deltacoronavirus strain USA IA 2014


id: cord-325611-tu1bn4hu
type: TAXON
entity:
  Human respiratory syncytial virus Human bocavirus Human metapneumovirus Adenovirus Human rubulavirus 1 4


id: cord-325611-tu1bn4hu
type: GGP
entity:
  Pneumoviridae Picornaviridae Paramyxoviridae Anelloviridae Coronaviridae Circoviridae Orthomyxoviridae


id: cord-325611-tu1bn4hu
type: ORG
entity:
  the Papillomaviridae Circoviridae Pneumoviridae Anelloviridae Picornaviridae Herpesviridae Totiviridae Virgaviridae


# bib

id: cord-003573-ekxq4l9a
title: Protection against homo and hetero-subtypic inﬂuenza A virus by optimized M2e DNA vaccine
author: Yao, Yanfeng
date: 2019-01-16
txt: ./txt/cord-003573-ekxq4l9a.txt
cache: ./cache/cord-003573-ekxq4l9a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455129/
doi: 10.1080/22221751.2018.1558962
summary:
  In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Our results show that the serum of mice immunized with p-tPA-p3M2e and p-p3M2e specifically binds to H1N1-infected MDCK cells, indicating that the M2e-specific antibodies induced by p-tPA-p3M2e and p-p3M2e immunization recognize the M2 protein on the surface of cells infected with influenza virus ( Figure S1 ). The above results demonstrate that vaccination with p-tPA-p3M2e protects mice from lethal infection with heterologous avian influenza strains, especially the H9N2 virus. In the present study, high antibody titers were induced in the p-tPA-p3M2e and p-p3M2e immunization groups, both of which demonstrated increased protection against challenge with homologous virus (H1N1). Immunization with p-tPA-p3M2e, without any adjuvant, induced high level, M2e-specific antibody production, humoral/cellular immune responses, and protected BALB/c mice from lethal infections of homo-and hetero-subtypic viruses.

abstract:
  Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.


id: cord-003676-kr4o8hoc
author: Tan, Chee Wah
date: 2019-05-28
txt: ./txt/cord-003676-kr4o8hoc.txt
cache: ./cache/cord-003676-kr4o8hoc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542153/
doi: 10.1080/22221751.2019.1621668
summary:
  title: Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs. Pteropine orthoreoviruses (PRVs) are a group of emerging bat-borne viruses, belonging to the genus Orthoreovirus within the family Reoviridae. Given the cross-species transmission of PRVs and frequent human-monkey interaction in Singapore and surrounding regions, we initiated this study to determine the seroprevalence of PRV3M in wild cynomolgus macaques and to examine the susceptibility of cynomolgus macaques to experimental infection with PRV3M and their potential role in acting as hosts facilitating cross-species transmission.

title:
  Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans

abstract:
  Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.


id: cord-264267-weat0qs6
author: Kleine-Weber, Hannah
date: 2020-01-21
txt: ./txt/cord-264267-weat0qs6.txt
cache: ./cache/cord-264267-weat0qs6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1713705
doi: 10.1080/22221751.2020.1713705
summary:
  Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. For host cell entry, the surface unit, S1, of MERS-CoV S binds to the cellular type-II transmembrane protein dipeptidyl peptidase 4 (DPP4, CD26) [15] . For the binding studies with solMERS-S1-Fc, a similar protocol was followed as described for the analysis of DPP4 surface expression with the exceptions that sol-MERS-S1-Fc was used instead of the primary antibody (1:10 dilution in PBS/BSA) and that an AlexaFluor488conjugated anti-human antibody (goat, 1:500 dilution in PBS/BSA, ThermoFisher Scientific) was employed as the secondary antibody. Reduced MERS-CoV S-driven host cell entry is caused by inefficient S protein binding to DPP4 harboring polymorphic amino acid residues.

title:
  Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

abstract:
  Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.


id: cord-265067-ejpblc6y
title: H7N9 avian influenza virus - search and re-search
author: Wen, Yu-Mei
date: 2013-04-10
txt: ./txt/cord-265067-ejpblc6y.txt
cache: ./cache/cord-265067-ejpblc6y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26038459/
doi: 10.1038/emi.2013.18
abstract: nan
summary:
  China National Health and Family Planning Commission organized experts to do a comprehensive analysis based on the laboratory results, clinical manifestations of patients, epidemiological data, and concluded that the patients were infected with strains of H7N9 avian influenza virus. China National Health and Family Planning Commission notified the World Health Organization that a new H7N9 avian flu virus had caused lethal human infections in China (Gao RB et al., unpublished). The avian influenza viruses that have occasionally infected and caused disease in people without showing human adaptation comprise H5N1, H9N2, and a variety of H7 viruses. At the same time survey for H9N7 among wild birds and poultries has been carried out by the animal Centers for Disease Control and Prevention, and confirmed by the National Key Laboratory of Avian Influenza Institute in Harbin. Avian influenza A H5N1 virus: a continuous threat to humans Infection of immunocompromised patients by avian H9N2 influenza A virus


id: cord-266987-ikt8r2o1
title: Laboratory diagnosis of emerging human coronavirus infections – the state of the art
author: Loeffelholz, Michael J.
date: 2020-03-30
txt: ./txt/cord-266987-ikt8r2o1.txt
cache: ./cache/cord-266987-ikt8r2o1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32196430/
doi: 10.1080/22221751.2020.1745095
summary:
  The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. It must be appreciated that no matter how accurate and fast laboratory testing methods are, the diagnosis of viral pneumonias such as caused by SARS-CoV-2 involves collecting the correct specimen from the patient at the right time. The authors recommended to use serology to facilitate the diagnosis of SARS-CoV-2 infections when an NP swab specimen was collected inappropriately and the molecular assays were performed unsatisfactorily [42] . Several RT-PCR protocols for detection of SARS-CoV-2 RNA have been posted by the World Health Organization at https://www.who.int/emergencies/ diseases/novel-coronavirus-2019/technical-guidance/ laboratory-guidance. Considering the increased levels of mortality and infectivity associated with three novel-coronavirus outbreaks, these random-access, safe and simple tests, which offer fast and accurate detection and identification, are likely to have an immediate impact on prompt clinical and epidemiological decisions [7, 63] .

abstract:
  The three unprecedented outbreaks of emerging human coronavirus (HCoV) infections at the beginning of the twenty-first century have highlighted the necessity for readily available, accurate and fast diagnostic testing methods. The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. Newer laboratory methods are fast, highly sensitive and specific, and are gradually replacing the conventional gold standards. This presentation reviews the current laboratory methods available for testing coronaviruses by focusing on the coronavirus disease 2019 (COVID-19) outbreak going on in Wuhan. Viral pneumonias typically do not result in the production of purulent sputum. Thus, a nasopharyngeal swab is usually the collection method used to obtain a specimen for testing. Nasopharyngeal specimens may miss some infections; a deeper specimen may need to be obtained by bronchoscopy. Alternatively, repeated testing can be used because over time, the likelihood of the SARS-CoV-2 being present in the nasopharynx increases. Several integrated, random-access, point-of-care molecular devices are currently under development for fast and accurate diagnosis of SARS-CoV-2 infections. These assays are simple, fast and safe and can be used in the local hospitals and clinics bearing the burden of identifying and treating patients.


id: cord-269232-rhhmvnlp
title: First isolation of West Nile virus from a dromedary camel
author: Joseph, Sunitha
date: 2016-06-08
txt: ./txt/cord-269232-rhhmvnlp.txt
cache: ./cache/cord-269232-rhhmvnlp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27273223/
doi: 10.1038/emi.2016.53
summary:
  Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. [6] [7] [8] [9] [10] [11] [12] [13] In this article, we report the first isolation of WNV from a dromedary calf in the United Arab Emirates during the process of MERS-CoV screening and the results of the comparative genome and phylogenetic analysis. 20 Notably, 14 amino-acid residues in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a (Figure 3) , with the majority of these differences observed in the putative E and NS5 proteins.

abstract:
  Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection.


id: cord-270012-toompiz4
title: Enterovirus D68-associated respiratory and neurological illness in Spain, 2014–2018
author: González-Sanz, Rubén
date: 2019-10-01
txt: ./txt/cord-270012-toompiz4.txt
cache: ./cache/cord-270012-toompiz4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2019.1668243
doi: 10.1080/22221751.2019.1668243
summary:
  During 2014, enterovirus D68 (EV-D68) outbreaks were described globally, causing severe respiratory diseases in children and, in some cases, subsequent paralysis. In this study, the type characterization of enterovirus (EV) detected in respiratory illnesses and the epidemiology and clinical association of EV-D68 infections in Spain over a five-year period were described. Therefore, the objectives of the present study were first, to identify the genotype of the EV detected in clinical samples collected from hospitalized patients with different respiratory diseases over a 5-year period, and second, to describe the molecular epidemiology and clinical characteristics of EV-D68 infections in Spain. Regarding patients with neurological symptoms, eight children and one adult were diagnosed with meningitis or meningoencephalitis and the remaining eight children were finally described as acute flaccid paralysis (AFP) cases. Two cases of acute severe flaccid myelitis associated with enterovirus D68 infection in children

abstract:
  During 2014, enterovirus D68 (EV-D68) outbreaks were described globally, causing severe respiratory diseases in children and, in some cases, subsequent paralysis. In this study, the type characterization of enterovirus (EV) detected in respiratory illnesses and the epidemiology and clinical association of EV-D68 infections in Spain over a five-year period were described. A total of 546 EV-positive samples from hospitalized patients with respiratory infections were included. EV-D68 was the most frequently detected type (46.6%, 191/410 typed EV). Other EV from species A (25.1%), B (27.8%) and C (0.5%) were also identified. EV-D68 infections were more associated with bronchitis while EV-A/B types were more frequent in upper respiratory illness (p < 0.01). EV-D68 was also detected in patients with neurological symptoms (nine meningitis/meningoencephalitis and eight acute flaccid paralysis cases). Phylogenetic analysis of 3′-VP1 region showed most Spanish EV-D68 sequences from 2014 to 2016 belonged to subclades B2/B3, as other American and European strains circulating during the same period. However, those detected in 2017 and 2018 clustered to the emerged subclade D1. In summary, different EV can cause respiratory infections but EV-D68 was the most prevalent, with several strains circulating in Spain at least since 2014. Association between EV-D68 infection and neurological disease was also described.


id: cord-276914-44ji0g78
title: Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity
author: Chen, Weilie
date: 2020-02-26
txt: ./txt/cord-276914-44ji0g78.txt
cache: ./cache/cord-276914-44ji0g78.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32102625/
doi: 10.1080/22221751.2020.1732837
summary:
  However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Patient 3 (Figure 3(A) ) was transferred to the ICU directly on illness day 11 because of his severe condition, the 2019-nCoV virus was laboratory detected both in pharyngeal (Ct = 30 + 30) and blood samples (Ct = 37 + 39) on day 12, And his infection was confirmed by CDC on day 13. His disease advanced pretty fast and became severe on day 7 and he was transferred to ICU after his blood sample was detected to be virus-positive (Ct = 32 + 37). For patient 1, a high concentration of viral RNA (Ct = 23 + 27, on day 13) was detected in anal swab but not in pharyngeal (the same day) and blood (1 d ahead).

abstract:
  The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.


id: cord-279733-c0w9bw5u
author: Lui, Pak-Yin
date: 2016-04-20
txt: ./txt/cord-279733-c0w9bw5u.txt
cache: ./cache/cord-279733-c0w9bw5u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27094905/
doi: 10.1038/emi.2016.33
summary:
  title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response. In non-specialized epithelial cells as well as a subset of specialized immune cells that are susceptible to MERS-CoV infection, 16, 18, 27 type I IFN production is an important part of the host innate immune response and is initiated by ubiquitously expressed cytoplasmic viral sensors in the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) family in response to the detection of viral pathogen-associated molecular patterns such as double-stranded RNA (dsRNA). Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response

title:
  Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.


id: cord-281727-elartlro
title: Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient
author: Sun, Jing
date: 2020-05-18
txt: ./txt/cord-281727-elartlro.txt
cache: ./cache/cord-281727-elartlro.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1760144
doi: 10.1080/22221751.2020.1760144
summary:
  title: Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. A novel coronavirus SARS-CoV-2 emerged to cause a major outbreak of severe pneumonia in humans in China and has spread to over 100 other countries [1] . Although viral RNA can be detected in multiple organs in COVID-19 patients, infectious SARS-CoV-2 has only been isolated from respiratory specimens [3, 4] . The urine sample tested positive for SARS-CoV-2 RNA on day 12 post infection (p.i.) (February 5th) for the first time and had periodically showed positive results in RT-PCR test until March 6th. Although it is hard to determine whether the kidney, the testis or the bladder were infected and produced infectious virus from current study, isolation of infectious SARS-CoV-2 in urine raises the possibility of fecal/urine-respiratory transmission.

abstract:
  SARS-CoV-2 caused a major outbreak of severe pneumonia (COVID-19) in humans. Viral RNA was detected in multiple organs in COVID-19 patients. However, infectious SARS-CoV-2 was only isolated from respiratory specimens. Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. The virus isolated could infect new susceptible cells and was recognized by its’ own patient sera. Appropriate precautions should be taken to avoid transmission from urine.


id: cord-282140-teplpmi6
author: Horm, Srey Viseth
date: 2016-07-20
txt: ./txt/cord-282140-teplpmi6.txt
cache: ./cache/cord-282140-teplpmi6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/emi.2016.69
doi: 10.1038/emi.2016.69
summary:
  title: Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Serum samples were collected, after obtaining informed consent, from LBM workers at the start of the study (January 2013) to form a baseline, and 8 weeks after the three major national festivals shown by previous work to be associated with increased A/H5N1 circulation in markets: 25 Lunar New Year, week 6; Khmer New Year, week 15; Pchum Ben, week 40. 25 To our knowledge, AIVs were detected in Cambodian LBMs during 2013 at a higher frequency than any other study published previously, 25 5 6 7 9 11 12 13 14 15 16 17 19 21 23 25 27 29 31 33 35 37 38 39 40 41 42 Avian influenza viruses in Cambodian live-bird markets SV Horm et al chicken swabs positive for influenza A RNA.

title:
  Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections

abstract:
  Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.


id: cord-284125-35ghtmhu
title: Perspectives of public health laboratories in emerging infectious diseases
author: Chua, Kaw Bing
date: 2013-06-26
txt: ./txt/cord-284125-35ghtmhu.txt
cache: ./cache/cord-284125-35ghtmhu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26038473/
doi: 10.1038/emi.2013.34
summary:
  6 Emerging novel viruses are a major public health concern with the potential of causing high health and socioeconomic impacts, as has occurred with progressive pandemic infectious diseases such as human immunodeficiency viruses (HIV), the recent pandemic caused by the novel quadruple re-assortment strain of influenza A virus (H1N1), and more transient events such as the outbreaks of Nipah virus in 1998/1999 and severe acute respiratory syndrome (SARS) coronavirus in 2003. To minimize the health and socioeconomic impacts of emerging epidemic infectious diseases, major challenges must be overcome in the national and international capacity for early detection, rapid and accurate etiological identification (especially those caused by novel pathogens), rapid response and effective control (Figure 1 ). However, to develop and establish such an effective national public health capacity, especially the laboratory component to support infectious disease surveillance, outbreak investigation and early response, a good understanding of the concepts of emerging infectious diseases and an integrated country and regional public health laboratory system in accordance with the nature and type of emerging pathogens, especially novel ones, are highly recommended.

abstract:
  The world has experienced an increased incidence and transboundary spread of emerging infectious diseases over the last four decades. We divided emerging infectious diseases into four categories, with subcategories in categories 1 and 4. The categorization was based on the nature and characteristics of pathogens or infectious agents causing the emerging infections, which are directly related to the mechanisms and patterns of infectious disease emergence. The factors or combinations of factors contributing to the emergence of these pathogens vary within each category. We also classified public health laboratories into three types based on function, namely, research, reference and analytical diagnostic laboratories, with the last category being subclassified into primary (community-based) public health and clinical (medical) analytical diagnostic laboratories. The frontline/leading and/or supportive roles to be adopted by each type of public health laboratory for optimal performance to establish the correct etiological agents causing the diseases or outbreaks vary with respect to each category of emerging infectious diseases. We emphasize the need, especially for an outbreak investigation, to establish a harmonized and coordinated national public health laboratory system that integrates different categories of public health laboratories within a country and that is closely linked to the national public health delivery system and regional and international high-end laboratories.


id: cord-285965-mar8zt2t
author: Su, Liang
date: 2020-03-25
txt: ./txt/cord-285965-mar8zt2t.txt
cache: ./cache/cord-285965-mar8zt2t.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1744483
doi: 10.1080/22221751.2020.1744483
summary:
  This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Here, we report the clinical manifestations, laboratory test results, imaging characteristics, and treatment regimen of nine SARS-CoV-2 infected children and their families in Jinan, Shandong province to increase awareness of this disease, especially in children. A retrospective review was conducted of the clinical, lab tests, and radiologic findings for nine children and their families admitted to the Jinan Infectious Diseases Hospital identified to be nucleic acid-positive for SARS-CoV-2 from 24 January 2020 to 24 February 2020. All the patients were recorded with basic information and epidemiological histories [4] including (1) History of travel or residence in Wuhan and surrounding areas or other reported cases within 14 days of onset; (2) History of contact with new coronavirus infection (nucleic acid-positive) 14 days before onset; (3) history of contact with patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days before onset; (4) Cluster onset, along with disease condition changes.

title:
  The different clinical characteristics of corona virus disease cases between children and their families in China – the character of children with COVID-19

abstract:
  This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.


id: cord-288741-69pgy833
author: Yang, Yue-Lin
date: 2020-02-24
txt: ./txt/cord-288741-69pgy833.txt
cache: ./cache/cord-288741-69pgy833.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32090689/
doi: 10.1080/22221751.2020.1730245
summary:
  LLC-PK and ST cells were infected with PDCoV at a multiplicity of infection (MOI) of 10 in the presence or not of trypsin, and the virus released to the supernatant was collected at 12 and 24 hpi. Immunofluorescence assay LLC-PK and HEK293-APN cells were plated in 24-well plates, and when confluency reached 90%, cells were washed three times with PBS and infected with PDCoV at different MOI in the presence or not of trypsin. After seeding in 6-well plates and the confluency of each cells reached around 90%, PDCoV was used to infect LLC-PK (MOI = 0.5, 1 and 10) and ST cells (MOI = 1, 2 and 5), washed twice with PBS at 2 hpi, and then medium supplemented or not with 5 μg/ml trypsin was added. We first infected LLC-PK cells at different MOIs from 0.5-10, and evaluated PDCoV replication by analyzing the cells at 8, 12 and 24 hpi for the presence of the viral N protein.

title:
  Trypsin promotes porcine deltacoronavirus mediating cell-to-cell fusion in a cell type-dependent manner

abstract:
  Porcine deltacoronavirus (PDCoV) is a newly emerging threat to the global porcine industry. PDCoV has been successfully isolated using various medium additives including trypsin, and although we know it is important for viral replication, the mechanism has not been fully elucidated. Here, we systematically investigated the role of trypsin in PDCoV replication including cell entry, cell-to-cell membrane fusion and virus release. Using pseudovirus entry assays, we demonstrated that PDCoV entry is not trypsin dependent. Furthermore, unlike porcine epidemic diarrhea virus (PEDV), in which trypsin is important for the release of virus from infected cells, PDCoV release was not affected by trypsin. We also demonstrated that trypsin promotes PDCoV replication by enhancing cell-to-cell membrane fusion. Most importantly, our study illustrates two distinct spreading patterns from infected cells to uninfected cells during PDCoV transmission, and the role of trypsin in PDCoV replication in cells with different virus spreading types. Overall, these results clarify that trypsin promotes PDCoV replication by mediating cell-to-cell fusion transmission but is not crucial for viral entry. This knowledge can potentially contribute to improvement of virus production efficiency in culture, not only for vaccine preparation but also to develop antiviral treatments.


id: cord-290671-6p23qxb8
author: Jiang, Shibo
date: 2020-01-31
txt: ./txt/cord-290671-6p23qxb8.txt
cache: ./cache/cord-290671-6p23qxb8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1723441
doi: 10.1080/22221751.2020.1723441
abstract: nan
summary:
  We have recently designed and engineered a pan-CoV fusion inhibitor, EK1 peptide, which could inhibit infection of five human coronaviruses, including SARS-CoV and MERS-CoV, and three bat-SL-CoVs [7] . Intranasal application of EK1 peptide before or after viral challenge, EK1 peptide can protect human DPP4-transgenic mice from MERS-CoV infection, suggesting its potential prophylactic and therapeutic effect against 2019-nCoV infection. The recently developed SARS-CoV and MERS-CoV neutralizing monoclonal antibodies (mAbs) and nanobodies with protective efficacy are specific to the S1 subunit of S protein, particularly the RBD [5, [8] [9] [10] . One of the rapid approaches is to evaluate the currently available SARS-CoV neutralizing antibodies with cross-neutralizing and protection activity against 2019-nCoV infection. The spike protein of SARS-CoV-a target for vaccine and therapeutic development A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein

title:
  An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies


id: cord-291002-csao3flr
title: Broad neutralizing activity of a human monoclonal antibody against H7N9 strains from 2013 to 2017
author: Chen, Cong
date: 2018-11-14
txt: ./txt/cord-291002-csao3flr.txt
cache: ./cache/cord-291002-csao3flr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30425238/
doi: 10.1038/s41426-018-0182-2
summary:
  In this study, we describe a previously characterized human monoclonal antibody, HNIgGA6, obtained by isolating rearranged heavy-chain and light-chain genes from patients who had recovered from H7N9 infections. Recent studies have characterized several neutralizing antibodies from human donors that target different epitopes on viral HA proteins, such as CT149 18 , H7.167 19 , m826 20 , HNIgGD5 21 , and HNIgGA6 22 , all of which represent potential interventions in the event of an H7N9 pandemic. Previously, we reported that an H7N9-neutralizing antibody, HNIgGA6, recognized the viral receptor binding site (RBS) on HA1 23 . Human infections with recently-emerging highly pathogenic H7N9 avian influenza virus in China Human monoclonal antibodies targeting the haemagglutinin glycoprotein can neutralize H7N9 influenza virus Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin

abstract:
  H7N9 influenza virus has been circulating among humans for five epidemic waves since it was first isolated in 2013 in China. The recent increase in H7N9 infections during the fifth outbreak in China has caused concerns of a possible pandemic. In this study, we describe a previously characterized human monoclonal antibody, HNIgGA6, obtained by isolating rearranged heavy-chain and light-chain genes from patients who had recovered from H7N9 infections. HNIgGA6 recognized multiple HAs and neutralized the infectivity of 11 out of the 12 H7N9 strains tested, as well as three emerging HPAI H7N9 isolates. The only resistant strain was A/Shanghai/1/2013 (H7N9-SH1), which carries the avian receptor alleles 186V and 226Q in the sialic acid-binding pocket. The mAb broadly neutralized divergent H7N9 strains from 2013 to 2017 and represents a potential alternative treatment for H7N9 interventions.


id: cord-291076-p350i54m
title: The role of C5a in acute lung injury induced by highly pathogenic viral infections
author: Wang, Renxi
date: 2015-05-06
txt: ./txt/cord-291076-p350i54m.txt
cache: ./cache/cord-291076-p350i54m.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/emi.2015.28
doi: 10.1038/emi.2015.28
summary:
  Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. [1] [2] [3] In addition, the complement system has been implicated in the development of acute lung diseases induced by highly pathogenic viruses including influenza A virus H1N1, 4 H5N1, 5 H7N9, 6 severe acute respiratory syndrome coronavirus (SARS-Cov), 7 Middle East respiratory syndrome coronavirus (MERS-Cov). C5a-mediated release of reactive oxygen species C5a is a strong chemoattractant for neutrophils and monocytes; it then activates these cells to generate oxidative burst with release of 10 A study demonstrated that ROS are primary pathogenic molecules in pneumonia from mice infected with influenza virus. Inhibition of Complement Activation Alleviates Acute Lung Injury Induced by Highly Pathogenic Avian Influenza H5N1 Virus Infection

abstract:
  The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses.


id: cord-296511-y2vhh6oq
author: Zhang, YiMin
date: 2016-01-06
txt: ./txt/cord-296511-y2vhh6oq.txt
cache: ./cache/cord-296511-y2vhh6oq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26733380/
doi: 10.1038/emi.2016.1
summary:
  title: Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit 9 Hence, HH is likely one possible cause of severe liver impairment in A(H7N9)-infected patients with respiratory failure. Patients who met all of the following criteria were diagnosed as having HH according to previous reports 7, 8, 12 : (i) a massive but transient elevated ALT level (more than 20-fold the upper limit of normal (ULN)), (ii) the presence of respiratory, cardiac or circulatory failure and (iii) exclusion of other causes of liver injury. The extent of Hypoxic hepatitis in A(H7N9)-infected patients Y Zhang et al 2 ALT elevation was considerably higher in HH patients than in non-HH patients with liver injury (on admission, 1079.50 6 41.72 U/L vs. 8 H7N9 influenza-infected patients with chronic heart disease accompanying acute heart failure are at elevated risk of severe liver damage.

title:
  Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit

abstract:
  Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.


id: cord-297942-6wdwrttn
author: Li, Taisheng
date: 2020-03-14
txt: ./txt/cord-297942-6wdwrttn.txt
cache: ./cache/cord-297942-6wdwrttn.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1735265
doi: 10.1080/22221751.2020.1735265
summary:
  To standardize the clinical diagnosis and treatment, Peking Union Medical College Hospital (PUMCH) has established a working group and formulated the following operational recommendation regarding "Diagnosis and Clinical Management of Severe Acute Respiratory Syndrome Coronavirus 2 Infection" (V2.0). According to the definition of the National Health Commission [1] , patients in accordance with one of the following standards should be hospitalized and transferred to Beijing designated medical institution as soon as possible; (1) respiratory rate increased (≥30 per min) or dyspnoea; (2) oxygen saturation ≤ 95% when breathing ambient air, or arterial oxygen tension (PaO₂) over inspiratory oxygen fraction (FIO₂) of less than 300 mm Hg (1 mm Hg equals to 0.133 kPa); (3) lung imaging indicating multilobular lesions or progression of lesions over 50% within 48 h; (4) quick sequential organ failure assessment (qSOFA) score ≥2; (5) community-acquired pneumonia-65 (CURB-65) score ≥ 1; (6) combined pneumothorax; (7) other clinical conditions that require hospitalization.

title:
  Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0): Working Group of 2019 Novel Coronavirus, Peking Union Medical College Hospital

abstract:
  Since December 2019, China has been experiencing an outbreak of a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features include fever, coughing, shortness of breath, and inflammatory lung infiltration. China rapidly listed SARS-CoV-2-related pneumonia as a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, an operational recommendation for the diagnosis and management of SARS-CoV-2 infection is developed by Peking Union Medical College Hospital.


id: cord-300641-narpqgmj
title: Public’s early response to the novel coronavirus–infected pneumonia
author: Zhan, Siyi
date: 2020-03-03
txt: ./txt/cord-300641-narpqgmj.txt
cache: ./cache/cord-300641-narpqgmj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32122250/
doi: 10.1080/22221751.2020.1732232
abstract: nan
summary:
  To the editor: Originated from Wuhan city in central China and widely spread due to the mass migration for Lunar new year holiday, 17,000+ confirmed novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) cases with 350+ deaths have been identified in the country since December 2019 [1] [2] . Worried on the highly contagious virus that currently lacks effective treatments, 84.9% (83.6-86.2%) subjects (2619) felt "extremely" or "very" nervous about NCIP, and 75.1% (73.6-76.6%) believed that it was at least as terrible as the Severe Acute Respiratory Syndromes (SARS) or avian influenza. Adults living in urban areas had a better awareness of the knowledge on NCIP than those in rural areas (72.7% vs.66.1%, p < 0.001 Protective measures such as washing hands, wearing masks and exercising can effectively prevent people from getting infected [4] [5] . As the NCIP outbreak continues, further understanding of the infection will help to adjust strategies for public'' health education.


id: cord-304550-6j1pb1pu
author: Yongchen, Zhang
date: 2020-05-02
txt: ./txt/cord-304550-6j1pb1pu.txt
cache: ./cache/cord-304550-6j1pb1pu.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1756699
doi: 10.1080/22221751.2020.1756699
summary:
  Here, we conducted a serial investigation on 21 individuals infected with SARS-CoV-2 in two medical centres from Jiangsu Province, including 11 non-severe COVID-19 patients, and 5 severe COVID-19 patients and 5 asymptomatic carriers based on nucleic acid test and clinical symptoms. In this respective study, we serially analysed the virus RNA test results in swab samples, along with anti-SARS-CoV-2 IgM and IgG responses among 21 COVID-19 patients at the Second Hospital of Nanjing and the Affiliated Hospital of Xuzhou Medical University in Jiangsu Province, China. Our serial SARS-CoV-2 RNA testing identified a prolonged viral shedding for asymptomatic cases compared to COVID-19 patients, suggesting the importance of early identification and timely quarantine for these asymptomatic carriers. It is possible that significantly high level of SARS-CoV-2 viral load observed in severe cases [8, 9] drives an early antibody response produced by immediate activation of extrafollicular B cells during acute infection [10, 11] .

title:
  Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients

abstract:
  Effective strategy to mitigate the ongoing pandemic of 2019 novel coronavirus (COVID-19) require a comprehensive understanding of humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the emerging virus causing COVID-19. The dynamic profile of viral replication and shedding along with viral antigen specific antibody responses among COVID-19 patients started to be reported but there is no consensus on their patterns. Here, we conducted a serial investigation on 21 individuals infected with SARS-CoV-2 in two medical centres from Jiangsu Province, including 11 non-severe COVID-19 patients, and 5 severe COVID-19 patients and 5 asymptomatic carriers based on nucleic acid test and clinical symptoms. The longitudinal swab samples and sera were collected from these people for viral RNA testing and antibody responses, respectively. Our data revealed different pattern of seroconversion among these groups. All 11 non-severe COVID-19 patients and 5 severe COVID-19 patients were seroconverted during hospitalization or follow-up period, suggesting that serological testing is a complementary assay to nucleic acid test for those symptomatic COVID-19 patients. Of note, immediate antibody responses were identified among severe cases, compared to non-severe cases. On the other hand, only one were seroconverted for asymptomatic carriers. The SARS-CoV-2 specific antibody responses were well-maintained during the observation period. Such information is of immediate relevance and would assist COVID-19 clinical diagnosis, prognosis and vaccine design.


id: cord-304850-9xetsc2c
title: Virus ecology: a gap between detection and prediction
author: Drosten, Christian
date: 2013-05-22
txt: ./txt/cord-304850-9xetsc2c.txt
cache: ./cache/cord-304850-9xetsc2c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26038466/
doi: 10.1038/emi.2013.25
abstract: nan
summary:
  7, 8 These and other recent findings remind us of an important issue in viral reservoir ecology: non-persisting viruses are maintained on a social level, requiring large, dense and interconnected host groups for their perpetual transmission. 13 There are prominent examples of bat-borne viruses that can be passed between humans, including Ebola virus, Marburg virus, Nipah virus and the severe acute respiratory syndrome agent. However, there remains a large gap between the many studies describing novel reservoir-borne viruses and our capabilities to use this knowledge to predict or prevent future human disease outbreaks. 13 As we dig deeper into viral reservoir ecology, including its man-made modifications, we may find that changes in host populations affect the transmission and maintenance of viruses with possible consequences for their potential to infect humans (Figure 1 ). Habitat fragmentation Resource abundance Change of social structure Risk Virus replication / transmission Duration of excretion / infectivity Figure 1 Modification of viral maintenance optimum.


id: cord-312307-0hqqheho
title: Outbreaks of enterovirus D68 in Malaysia: genetic relatedness to the recent US outbreak strains
author: Ng, Kim Tien
date: 2015-08-05
txt: ./txt/cord-312307-0hqqheho.txt
cache: ./cache/cord-312307-0hqqheho.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26421270/
doi: 10.1038/emi.2015.47
abstract: nan
summary:
  Specimens positive for enteroviruses were further confirmed using standard molecular approaches that involved amplification and sequencing of the human enterovirus VP4/VP2 gene using primers described previously. Based on previously described EV-D68 classification, 11 the newly sequenced strains from Malaysia were found within clade A (MY-Cluster-1) and clade B (MY-Cluster-2). Phylogenetic analysis of the P1 region indicated that 91.7% (11/12) of the Malaysian EV-D68 formed clusters, suggesting the transient EV-D68 outbreaks were most likely caused by at least two viral lineages ( Figure 1) . Such observation suggests an ongoing ''''clade shift'''' or lineage replacement of circulating EV-D68 in causing new outbreak, as observed in other enterovirus-associated outbreaks. Our data suggest that the recent EV-D68 strains associated with unprecedented severe respiratory outbreaks in the USA in 2014 were probably descended from the recent EV-D68 lineages circulating in Thailand and Malaysia. Seven strains of enterovirus D68 detected in the United States during the 2014 severe respiratory disease outbreak


id: cord-314189-0rg6n7fr
title: Intranasal application of polyethyleneimine suppresses influenza virus infection in mice
author: He, Biao
date: 2016-04-27
txt: ./txt/cord-314189-0rg6n7fr.txt
cache: ./cache/cord-314189-0rg6n7fr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/emi.2016.64
doi: 10.1038/emi.2016.64
abstract: nan
summary:
  2 Therefore, we hypothesized that intranasal application of a mucosal stimulant that induces antiviral cytokines, except IL-17, may be effective against influenza virus infection. We then examined the viral titers in mouse lungs as previously described 5 and found that PEI significantly reduced lung viral titers on day 2 after H1N1 challenge, whereas the viral titers in the lungs of mice in the CTB-and PBS-pretreated groups showed no significant differences ( Figure 1C ). These results suggest that intranasal application of PEI has efficacy in protecting mice from challenge by influenza virus H1N1. To elucidate the mechanism of action of PEI, we examined the RNA levels of IFN-α4, IFN-β, IFN-γ, GM-CSF, IFITM3 and IL-17 in the lungs of mice pretreated with PEI, CTB, and PBS, respectively, before viral challenge using quantitative reverse transcription-PCR (qRT-PCR). In summary, we demonstrated that PEI, a mucosal stimulant for topical intranasal administration, is highly effective in preventing influenza virus infection.


id: cord-314254-9ye8tfvz
title: Natural reservoirs for homologs of hepatitis C virus
author: Pfaender, Stephanie
date: 2014-03-26
txt: ./txt/cord-314254-9ye8tfvz.txt
cache: ./cache/cord-314254-9ye8tfvz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/emi.2014.19
doi: 10.1038/emi.2014.19
summary:
  To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaciand pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Non-primate hepaciviruses (NPHV) were initially discovered in domestic dogs and subsequently in horses 12, 13 and other diverse and widespread HCV-like viruses have been reported in wild populations of rodents and bats. Furthermore, liver function analyses revealed no indication for hepatic inflammation as c-glutamyl transferase and glutamate dehydrogenase values were within reference range, with the exception of a mildly elevated c-glutamyl transferase New HCV-like viruses in different mammalian hosts Pfaender et al 4 level in one horse.

abstract:
  Hepatitis C virus is considered a major public health problem, infecting 2%–3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen.


id: cord-314350-kcatqzgs
title: An emerging novel goose astrovirus associated with gosling gout disease, China
author: Zhang, Xinyu
date: 2018-09-05
txt: ./txt/cord-314350-kcatqzgs.txt
cache: ./cache/cord-314350-kcatqzgs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30185786/
doi: 10.1038/s41426-018-0153-7
summary:
  Through in vitro and in vivo experiments, we identified and isolated a novel goose astrovirus different from the CAstVas a causative agent of the gout disease recently circulating in gosling flocks in China. To isolate the novel goose astrovirus, the homogenates of the pooled liver and kidney from the diseased gosling were inoculated into chicken liver cell line LMH. To further confirm the isolation of the virus, the infected LMH cells were analyzed through indirect fluorescent assay (IFA) using the convalescent sera from the survival geese with gout symptom and the mouse sera against the capsid P2 of GD (generated in our laboratory) respectively. Different from those recently reported by other groups, we efficiently isolate such novel goose astrovirus in vitro using the cell culture system (LMH cells) and reproduce the associated gout disease by inoculating the cell cultured virus GD.

abstract:
  Since the first isolation from human, astroviruses have been detected in many species. Wide host range and occasional cross-transmission of astrovirus pose a risk for zoonotic infection. Here, novel astroviruses were identified from goslings with recent epidemic gout disease in China. A virus, designated as GD, was efficiently isolated from a diseased gosling using LMH cells. Genome of GD amplified using 5′ and 3′ RACE was 7183nt in full length. Sequence analysis revealed the genome of GD was <60.8% homology with others deposited in Genbank. Moreover, GD could be neutralized by goose convalescent sera, and the gout associated symptom in goslings could be reproduced by GD infection. Our data demonstrated the goose astrovirus could be one of the causative agents of the ongoing gosling gout disease in China. The identification of the goose astrovirus not only diversified the astrovirus species, but also broadened the disease patterns caused by astroviruses.


id: cord-314574-3e6u4aza
author: Tian, Xiaolong
date: 2020-02-17
txt: ./txt/cord-314574-3e6u4aza.txt
cache: ./cache/cord-314574-3e6u4aza.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1729069
doi: 10.1080/22221751.2020.1729069
summary:
  Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD. Next, we expressed and purified several representative SARS-CoV-specific antibodies which have been reported to target RBD and possess potent neutralizing activities, including m396 [3] , CR3014 [4] , CR3022 [5] , as well as a MERS-CoV-specific human monoclonal antibody m336 developed by our laboratory [15] , and measured their binding ability to 2019-nCoV RBD by ELISA (Figure 1(e)) .

title:
  Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

abstract:
  The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.


id: cord-315355-a25ba7dz
author: Chen, Qi
date: 2018-06-06
txt: ./txt/cord-315355-a25ba7dz.txt
cache: ./cache/cord-315355-a25ba7dz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41426-018-0108-z
doi: 10.1038/s41426-018-0108-z
abstract: nan
summary:
  The four SpDCoV strains identified in this study share a slightly higher identity (94.4-94.6% and 96.0-96.4%) to a sparrow CoV strain HKU17-6124 than to PDCoV strains (93.4-93.6% and 95.3-95.8%) in their ORF1ab and N proteins, respectively ( Fig. 1b and Supplementary Table S2 ). In contrast, the four SpDCoV strains share a significantly lower identity to sparrow CoV HKU17 (58.2-58.6%) than to three PDCoV strains (82.7-87.7%) in their S protein (Fig. 1b and Supplementary Table S2 ). In addition, they share a relatively lower identity (90.7-91.5% and 93.5-95.5%) to sparrow CoV HKU17 than the PDCoV strains (94.9-95.8% and 96.1-98.1%) in their E and M proteins, respectively (Supplementary Table S2 ). These findings were also confirmed by phylogenetic tree analysis of amino-acid sequences in which the four SpDCoV strains clustered together and were closely related to PDCoV and sparrow CoV HKU17 strains in ORF1ab, E, M, and N trees ( Fig. 1c and Supplementary Figure S1 ).

title:
  The emergence of novel sparrow deltacoronaviruses in the United States more closely related to porcine deltacoronaviruses than sparrow deltacoronavirus HKU17


id: cord-318392-r9bbomvk
author: Woo, Patrick CY
date: 2017-06-21
txt: ./txt/cord-318392-r9bbomvk.txt
cache: ./cache/cord-318392-r9bbomvk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28634353/
doi: 10.1038/emi.2017.37
summary:
  The genomes of two Coronavirus HKU15 strains detected in the nasopharyngeal samples of two different pigs were sequenced following our previous publications 26, 27 with modifications. Divergence times for the Coronavirus HKU15 strains were calculated based on the complete genome sequence data, utilizing the Bayesian Markov chain Monte Carlo method using BEAST 1.8.0 33 with the substitution model GTR (general time-reversible model)+G (gammadistributed rate variation)+I (estimated proportion of invariable sites), a strict molecular clock, and a constant coalescent. In one (S579N) of the two Coronavirus HKU15 genomes that we sequenced in this study, variant sites were observed at four positions; two of them were due to nucleotide substitutions, and the other two were results of indels at mononucleotide polymeric regions (189th and 376th bases).

title:
  Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region

abstract:
  Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.


id: cord-325611-tu1bn4hu
author: Pérez-Sautu, Unai
date: 2019-07-23
txt: ./txt/cord-325611-tu1bn4hu.txt
cache: ./cache/cord-325611-tu1bn4hu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31335277/
doi: 10.1080/22221751.2019.1640587
summary:
  We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT–PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. In this report, we performed a systematic study of respiratory specimens collected from a carefully characterized and highly representative, prospective cohort of pediatric cases suffering unexplained ARI, and we compared the rate of detection of pathogens by utilizing validated molecular assays, and a comprehensive sequence-independent, high-throughput sequencing-based analysis. In order to assess for the clinical relevance of the viral identifications made by HTS in the specimens collected from the unexplained cases of respiratory infections, a second cohort of age-matched healthy individuals from the same epidemiologic environment was also studied with the same methodology. Respiratory viral pathogens identified by target-agnostic HTS analysis and confirmed by contig-specific molecular assays in the respiratory specimens from the cases of respiratory infection and from the control group.

title:
  Target-independent high-throughput sequencing methods provide evidence that already known human viral pathogens play a main role in respiratory infections with unexplained etiology

abstract:
  Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT–PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.


id: cord-325969-9zhmmvdg
title: Additional molecular testing of saliva specimens improves the detection of respiratory viruses
author: To, Kelvin KW
date: 2017-06-07
txt: ./txt/cord-325969-9zhmmvdg.txt
cache: ./cache/cord-325969-9zhmmvdg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28588283/
doi: 10.1038/emi.2017.35
summary:
  In the first cohort of 159 patients whose nasopharyngeal aspirates (NPAs) tested positive for respiratory viruses during routine testing, the viral load was measured using quantitative reverse transcription PCR. Although NPAs have high viral loads and remain the specimen of choice for most patients with respiratory virus infections, supplementary molecular testing of saliva can improve the clinical management of these patients. The first part of the study consisted of patients whose NPA samples tested positive for respiratory viruses by DFA or the influenza A virus M gene by real-time RT-PCR during routine respiratory virus testing in our clinical microbiology laboratory ( Figure 1 ). In the first part of this study, saliva had a higher viral load than NPA in 17.0% of the patients who tested positive for respiratory viruses by DFA or influenza A virus by RT-PCR in their NPA samples.

abstract:
  Emerging infectious diseases in humans are often caused by respiratory viruses such as pandemic or avian influenza viruses and novel coronaviruses. Microbiological testing for respiratory viruses is important for patient management, infection control and epidemiological studies. Nasopharyngeal specimens are frequently tested, but their sensitivity is suboptimal. This study evaluated the incremental benefit of testing respiratory viruses in expectorated saliva using molecular assays. A total of 258 hospitalized adult patients with suspected respiratory infections were included. Their expectorated saliva was collected without the use of any special devices. In the first cohort of 159 patients whose nasopharyngeal aspirates (NPAs) tested positive for respiratory viruses during routine testing, the viral load was measured using quantitative reverse transcription PCR. Seventeen percent of the patients (27/159) had higher viral loads in the saliva than in the NPA. The second cohort consisted of 99 patients whose NPAs tested negative for respiratory viruses using a direct immunofluorescence assay. Their NPA and saliva specimens were additionally tested using multiplex PCR. In these patients, the concordance rate by multiplex PCR between NPA and saliva was 83.8%. Multiplex PCR detected viruses in saliva samples from 16 patients, of which nine (56.3%) had at least one virus that was not detected in the NPA. Decisions on antiviral or isolation precautions would be affected by salivary testing in six patients. Although NPAs have high viral loads and remain the specimen of choice for most patients with respiratory virus infections, supplementary molecular testing of saliva can improve the clinical management of these patients.


id: cord-326512-iex98lr1
author: Niu, Xuefeng
date: 2019-05-25
txt: ./txt/cord-326512-iex98lr1.txt
cache: ./cache/cord-326512-iex98lr1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31130109/
doi: 10.1080/22221751.2019.1614885
summary:
  title: Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. The SHM rates of these heavy chains compared with their predicted germline sequences were relatively low, at 4.51% for 7B3H, 3.47% for 1C11H, and 4.17% for 6A6H, which is lower than that of antibodies isolated from annual trivalent inactivated influenza vaccine (TIV) donors [34] and chronic human immunodeficiency virus (HIV)-1 patients (>30%) [27, 35] . In a separate experiment, an unrelated mAb, 2G11, which is specific for H7N9 influenza virus, showed no protective effects on ZIKV-infected neonatal SCID mice (data not shown). Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

title:
  Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model

abstract:
  The Zika virus (ZIKV) outbreak and its link to microcephaly triggered a public health concern. To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. Three mAbs (7B3, 1C11, and 6A6) that showed the most potent and broad neutralization activities against the African, Asian, and American strains were selected for further analysis. mAb 7B3 showed an IC50 value of 11.6 ng/mL against the circulating American strain GZ02. Epitope mapping revealed that mAbs 7B3 and 1C11 targeted residue K394 of the lateral ridge (LR) epitope of the EDIII domain, but 7B3 has a broader LR epitope footprint and recognizes residues T335, G337, E370, and N371 as well. mAb 6A6 recognized residues D67, K118, and K251 of the EDII domain. Interestingly, although the patient was seronegative for DENV infection, mAb 1C11, originating from the VH3-23 and VK1-5 germline pair, neutralized both ZIKV and DENV1. Administration of the mAbs 7B3, 1C11, and 6A6 protected neonatal SCID mice infected with a lethal dose of ZIKV. This study provides potential therapeutic antibody candidates and insights into the antibody response after ZIKV infection.


id: cord-327024-1k5jucae
title: Isolation and characterization of an astrovirus causing fatal visceral gout in domestic goslings
author: Zhang, Qingshui
date: 2018-04-19
txt: ./txt/cord-327024-1k5jucae.txt
cache: ./cache/cord-327024-1k5jucae.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29674726/
doi: 10.1038/s41426-018-0074-5
summary:
  18 reported the detection of avian nephritis virus infection in Croatian goose flocks and provided evidence that this AstV was associated with stunting and prehatching mortality of goose embryos. To determine the potential genetic mutation(s) that might occur during the goose embryo passage, the initial virus genome was sequenced using the total RNA extracted from the clinical case tissue homogenate. When the samples were tested by RT-PCR for virus shedding evaluation, the AAstV specific RNA was sequentially detected from the cloacal swabs of infected goslings from 2 to 12 dpi (Fig. 6 ). To evaluate the potential adaptive mutation (s) of the virus that might occur during the process of goose embryo passage, we sequenced the complete genome of initial virus using the total RNA extracted from the clinical case tissue homogenate of kidney, spleen, and liver using the method described above.

abstract:
  Astroviruses are recognized as a leading cause of gastroenteritis in humans and animals. They are also associated with extra-intestinal diseases, such as hepatitis in ducklings, nephritis in chickens, and encephalitis in cattle. In February 2017, a fatal infection of goslings characterized by visceral urate deposition was reported in the Shandong province, China. Our systematic investigation led to the isolation of an astrovirus, designated AAstV/Goose/CHN/2017/SD01, and similar disease was reproduced by experimental infection of healthy goslings, fulfilling Koch’s postulates. The isolated astrovirus replicated well and resulted in 100% mortality of goose embryos. Complete genome sequence analysis revealed that the isolate was genetically distinct from known astroviruses and closely related to members of the avastrovirus genogroup II. Experimental infection showed that the isolate was highly pathogenic in goslings, causing clinical signs, growth repression and in many cases mortality. Histopathological examination indicated that lesions occurred mainly in the kidneys of infected birds. However, virus-specific genomic RNA was detected in all representative tissues, and virus shedding was detected up to 12 days after inoculation, suggesting that the isolate was able to spread systemically and replicate efficiently in vivo. Collectively, our study demonstrates, for the first time, the etiological role of a genetically distinct astrovirus in the fatal infection of goslings.


id: cord-327499-4aps0kvp
author: Zhang, Wei
date: 2020-02-17
txt: ./txt/cord-327499-4aps0kvp.txt
cache: ./cache/cord-327499-4aps0kvp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1729071
doi: 10.1080/22221751.2020.1729071
summary:
  It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Human samples, including oral swabs, anal swabs and blood samples were collected by Wuhan pulmonary hospital with the consent from all patients and approved by the ethics committee of the designated hospital for emerging infectious diseases. We conducted a molecular investigation to patients in Wuhan pulmonary hospital, who were detected as oral swabs positive for 2019-nCoV upon admission. We collected blood, oral swabs and anal swabs for 2019-nCoV qPCR test using previously established method [5] . We detected the virus in oral swabs, anal swabs and blood, thus infected patients can potentially shed this pathogen through respiratory, fecal-oral or body fluid routes. Above all, we strongly suggest using viral IgM and IgG serological test to confirm an infection, considering the unreliable results from oral swabs detection.

title:
  Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes

abstract:
  In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.


id: cord-329555-y3cp5wza
author: Negrey, Jacob D.
date: 2019-01-21
txt: ./txt/cord-329555-y3cp5wza.txt
cache: ./cache/cord-329555-y3cp5wza.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30866768/
doi: 10.1080/22221751.2018.1563456
summary:
  Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. Here, we report simultaneous outbreaks of respiratory disease in two nearby chimpanzee communities in Uganda, caused by two distinct negative-sense RNA viruses of human origin. Human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3) was detected in 5 of 14 individuals (35.7%) from Kanyawara chimpanzees exhibiting clinical signs during, but not before, the outbreak period (Fisher''s exact P = 0.0005). For example, HRV3 can cause upper respiratory disease and predispose chimpanzees to invasive pneumococcal infection [44] , and the bacterium Streptococcus pneumoniae co-occurs with human metapneumoviruses and respiratory syncytial viruses in both wild and in captive apes [9, 22] .

title:
  Simultaneous outbreaks of respiratory disease in wild chimpanzees caused by distinct viruses of human origin

abstract:
  Respiratory viruses of human origin infect wild apes across Africa, sometimes lethally. Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. The viruses were absent before the outbreaks, but each was present in ill chimpanzees from one community during the outbreak period. Clinical signs and gross pathologic changes in affected chimpanzees closely mirrored symptoms and pathology commonly observed in humans for each virus. Epidemiologic modelling showed that MPV and HRV3 were similarly transmissible (R(0) of 1.27 and 1.48, respectively), but MPV caused 12.2% mortality mainly in infants and older chimpanzees, whereas HRV3 caused no direct mortality. These results are consistent with the higher virulence of MPV than HRV3 in humans, although both MPV and HRV3 cause a significant global disease burden. Both viruses clustered phylogenetically within groups of known human variants, with MPV closely related to a lethal 2009 variant from mountain gorillas (Gorilla beringei beringei), suggesting two independent and simultaneous reverse zoonotic origins, either directly from humans or via intermediary hosts. These findings expand our knowledge of human origin viruses threatening wild chimpanzees and suggest that such viruses might be differentiated by their comparative epidemiological dynamics and pathogenicity in wild apes. Our results also caution against assuming common causation in coincident outbreaks.


id: cord-336157-aqc9zrrm
author: Liang, Guodong
date: 2015-03-25
txt: ./txt/cord-336157-aqc9zrrm.txt
cache: ./cache/cord-336157-aqc9zrrm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26038768/
doi: 10.1038/emi.2015.18
summary:
  Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. [2] [3] Chikungunya virus (CHIKV), West Nile virus (WNV) and dengue virus (DENV) are three of a large number of neglected human pathogenic arthropod-borne viruses (arboviruses) whose combined figures for morbidity and mortality far exceed those for Ebola, severe acute respiratory syndrome and Middle East respiratory syndrome viruses. However, many other arthropod species, in which viruses have been identified, may be involved in perpetuating the virus life cycle without having been associated with overt disease in humans or animals. 55 However, implementation of temporary localized arthropod control measures during epidemics, for example in high density urbanized areas, can still play an important but transient role in reducing the impact on humans and animals of emerging arboviruses.

title:
  Factors responsible for the emergence of arboviruses; strategies, challenges and limitations for their control

abstract:
  Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.


id: cord-336671-vfq5ft08
author: Ai, Jing-Wen
date: 2020-03-16
txt: ./txt/cord-336671-vfq5ft08.txt
cache: ./cache/cord-336671-vfq5ft08.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1080/22221751.2020.1738905
doi: 10.1080/22221751.2020.1738905
summary:
  Unexplained pneumonia (UP) caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged in China in late December 2019 and has infected more than 9000 cases by 31 January 2020. A combinative approach of real-time RT–PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) were used to diagnose this unexplained pneumonia patient. The reasons behind this outbreak are numerous, the highly infectious nature of SARS-CoV-2, limited pathogen detection method for unexplained pneumonia, the high population density of the Hubei Province and across China, etc. On 20 January, Shanghai reported the first imported case of SARS-CoV-2 infection, and through this case, we seek a combinative approach of selected techniques to improve pathogen identification of unexplained pneumonia in the future. We then performed real-time RT-PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) on her respiratory sample and finally diagnosed her with COVID-19.

title:
  Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned

abstract:
  Unexplained pneumonia (UP) caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged in China in late December 2019 and has infected more than 9000 cases by 31 January 2020. Shanghai reported the first imported case of COVID-19 (Coronavirus Disease 2019) in 20 January 2020. A combinative approach of real-time RT–PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) were used to diagnose this unexplained pneumonia patient. Real-time RT–PCR and CRISPR-based assay both reported positive. This sample belonged to Betacoronavirus and shared a more than 99% nucleotide (nt) identity with the Wuhan SARS-CoV-2 isolates. We further compared pros and cons of common molecular diagnostics in UP. In this study, we illustrated the importance of combining molecular diagnostics to rule out common pathogens and performed mNGS to obtain unbiased potential pathogen result for the diagnosis of UP.


id: cord-343196-vlwzzrgc
title: Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017
author: Kiambi, Stella
date: 2018-11-28
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url: https://www.ncbi.nlm.nih.gov/pubmed/30482895/
doi: 10.1038/s41426-018-0193-z
abstract: nan
summary:
  The MERS-CoV RNA-positive animals belonged to two different dromedary camel herds in Dabel and Lombolio, which are both located within Isiolo country. To experimentally confirm the presence of two independently circulating MERS-CoV strains and to rule out sample cross-contamination, we generated complete MERS-CoV genome sequences using a previously established protocol 10 . Other confirmed MERS-CoVpositive samples were assigned to two different MERS-CoV isolates ("Dabel" or "Lombolio") by amplifying and sequencing single-nucleotide polymorphisms in the spike gene and the open reading frame 3 (Supplementary Table) . The previously described clade C African MERS-CoV strains 4,5 had several mutations in the spike protein, which is responsible for cellular receptor interaction, virus entry, and antibody-directed virus neutralization 12 . An explanation for this observation may again be a lack of testing of imported animals and/or the fact that previous clade A/B MERS-CoV infections may have established herd immunity in the Arabian dromedary populations.


id: cord-349956-h4i2t2cr
author: Hoang, Van-Thuan
date: 2019-11-21
txt: ./txt/cord-349956-h4i2t2cr.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/31749410/
doi: 10.1080/22221751.2019.1693247
summary:
  We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. showed that human rhinovirus (HRV) and influenza viruses were the most common viral respiratory pathogens isolated from ill Hajj pilgrims [6] . Unadjusted associations between respiratory pathogen carriage with multiples factors: sociodemographic characteristics (gender, ≥60 years), chronic respiratory disease, BMI classification, smoking status; individual preventive measures (vaccination against influenza, vaccination against IPD, use of a face mask, hand washing, disinfectant gel and disposable handkerchiefs); antibiotic intake 10 days before each sample; respiratory virus or bacteria and dual carriage were analysed by univariable analysis. aureus carriage increase and the initial wave of respiratory symptoms, suggests that this pathogen association was responsible for the RTIs that affected most pilgrims soon after arriving in Mecca.

title:
  The dynamics and interactions of respiratory pathogen carriage among French pilgrims during the 2018 Hajj

abstract:
  We conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (LRTI) among French pilgrims during the 2018 Hajj. Each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in Saudi Arabia. Carriage of the main respiratory pathogens was assessed by PCR. 121 pilgrims were included and 93.4% reported respiratory symptoms during the study period. The acquisition of rhinovirus, coronaviruses and Staphylococcus aureus occurred soon after arrival in Saudi Arabia and rates decreased gradually after days 5 and 6. In contrast, Streptococcus pneumoniae and Klebsiella pneumoniae carriage increased progressively until the end of the stay in Saudi Arabia. Haemophilus influenzae and Moraxella catarrhalis carriage increased starting around days 12 and 13, following an initial clearance. Influenza viruses were rarely isolated. We observed an independent positive mutual association between S. aureus and rhinovirus carriage and between H. influenzae and M. catarrhalis carriage. Dual carriage of H. influenzae and M. catarrhalis was strongly associated with S. pneumoniae carriage (OR = 6.22). Finally, our model showed that M. catarrhalis carriage was negatively associated with K. pneumoniae carriage. Chronic respiratory disease was associated with symptoms of LRTI. K. pneumoniae, M. catarrhalis-S. aureus and H. influenzae-rhinovirus dual carriage was associated with LRTI symptoms. Our data suggest that RTIs at the Hajj are a result of complex interactions between a number of respiratory viruses and bacteria.


id: cord-354546-lgkqwm6u
author: Yin, Yingxian
date: 2016-09-07
txt: ./txt/cord-354546-lgkqwm6u.txt
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url: https://doi.org/10.1038/emi.2016.100
doi: 10.1038/emi.2016.100
summary:
  7 By far, Aedes aegypti is considered the principal transmission vector of ZIKV, 8 although Aedes albopictus, which caused several outbreaks of dengue fever in Guangdong Province of South China in the last two decades, may play a role in the spread of this virus because A. These four infected individuals were first confirmed by real-time reversetranscription polymerase chain reaction (RT-PCR) in Baiyun International Airport of Guangzhou, where the youngest one (the son) had developed fever, and the family was then isolated by the local department of public health. 28 A previous study Figure 4 Phylogenetic tree based on E gene sequences of Zika virus isolates. First imported familial ZIKV cases in China Y Yin et al showed that a patient had prolonged shedding of viral RNA in saliva and urine for up to 29 days after symptom onset. In previous research, E gene sequences of ZIKV isolates were usually utilized to construct phylogenetic trees 19 based on experience from molecular study of dengue virus.

title:
  Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission

abstract:
  Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that can potentially threaten South China. A Chinese family of four returning from Venezuela to China was found to be positive for ZIKV when the youngest son's fever was first detected at an airport immigration inspection. They were isolated temporarily in a local hospital in Enping city, Guangdong province, where their clinical data were recorded and urine and saliva were collected to isolate ZIKV and to obtain viral sequences. All of them except the mother presented mild symptoms of rash and fever. Envelope gene sequences from the father, daughter and son were completely identical. Phylogenetic analysis demonstrated that this strain is similar to several imported strains reported in recent months, which are all clustered into a group isolated from 2015 ZIKA outbreaks in Brazil. Together with the climatic features in Venezuela, New York and Guangdong in February, it can be concluded that our subjects are imported cases from Venezuela. With the same viral sequence being shared between family members, neither direct human-to-human nor vector transmission can be ruled out in this study, but the former seems more likely. Although our subjects had mild illness, epidemiologists and public health officials should be aware of the risk of further expansion of ZIKV transmission by local competent vectors.


id: cord-354790-xx6imhzb
author: Lambour, Jennifer
date: 2016-08-17
txt: ./txt/cord-354790-xx6imhzb.txt
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url: https://doi.org/10.1038/emi.2016.97
doi: 10.1038/emi.2016.97
summary:
  31 In addition to controlling the viral propagation by these mechanisms, the opsonization of viral particles and/or infected cells by therapeutic antiviral mAbs of the IgG type leads to the formation of immune complexes (ICs) recognizable by the FcγRs expressed on antigen-presenting cells (APCs) such as DCs. This can potentially affect the endogenous antiviral adaptive immune response of passive immunotherapy-treated individuals. Moreover, as the in vivo activity of anti-HIV-1 bNAbs, including viral load control, was recently shown to crucially depend on Fc effector functions, 53,54 an important issue is identifying that Fc-FcγRs interactions are involved in the induction of vaccinelike effects by antiviral mAbs. To understand the mechanisms underlying the enhancement of antiviral responses by ICs, several in vitro studies have addressed whether antibody-mediated viral uptake by DCs could lead to stronger activation of these cells and the development of stronger virus-specific CD4 + and CD8 + T-cell responses in an Fc-dependent manner.

title:
  Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

abstract:
  Monoclonal antibodies (mAbs), which currently constitute the main class of biotherapeutics, are now recognized as major medical tools that are increasingly being considered to fight severe viral infections. Indeed, the number of antiviral mAbs developed in recent years has grown exponentially. Although their direct effects on viral blunting have been studied in detail, their potential immunomodulatory actions have been overlooked until recently. The ability of antiviral mAbs to modulate antiviral immune responses in infected organisms has recently been revealed. More specifically, upon recognition of their cognate antigens, mAbs form immune complexes (ICs) that can be recognized by the Fc receptors expressed on different immune cells of infected individuals. This binding may be followed by the modulation of the host immune responses. Harnessing this immunomodulatory property may facilitate improvements in the therapeutic potential of antiviral mAbs. This review focuses on the role of ICs formed with different viral determinants and mAbs in the induction of antiviral immune responses in the context of both passive immunotherapies and vaccination strategies. Potential deleterious effects of ICs on the host immune response are also discussed.


