#Genomic #Characterization of the 2019 Novel Human-Pathogenic #Coronavirus Isolated From a #Patient With Atypical #Pneumonia After Visiting #Wuhan (Emerg Microbes Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Emerg Microbes Infect, 9 (1), 221-236 Dec 2020

Genomic Characterization of the 2019 Novel Human-Pathogenic Coronavirus Isolated From a Patient With Atypical Pneumonia After Visiting Wuhan

Jasper Fuk-Woo Chan 1 2 3 4, Kin-Hang Kok 1 3 4, Zheng Zhu 3, Hin Chu 1 3 4, Kelvin Kai-Wang To 1 2 3 4, Shuofeng Yuan 1 3 4, Kwok-Yung Yuen 2 3 4

Affiliations: 1 State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. 2 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China. 3 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. 4 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

PMID: 31987001  DOI: 10.1080/22221751.2020.1719902

 

Abstract

A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

Keywords: Coronavirus; SARS; Wuhan; bioinformatics; emerging; genome; respiratory; virus.

Keywords: 2019-nCoV; Human; Bats.

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Specificity, #Kinetics and Longevity of #Antibody #Responses to #Avian #Influenza A(#H7N9) Virus #Infection in #Humans (J Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect. 2020 Jan 16. pii: S0163-4453(20)30025-6. doi: 10.1016/j.jinf.2019.11.024. [Epub ahead of print]

Specificity, Kinetics and Longevity of Antibody Responses to Avian Influenza A(H7N9) Virus Infection in Humans.

Chen J1, Zhu H2, Horby PW3, Wang Q1, Zhou J1, Jiang H4, Liu L5, Zhang T6, Zhang Y7, Chen X1, Deng X1, Nikolay B8, Wang W1, Cauchemez S8, Guan Y2, Uyeki TM9, Yu H10.

Author information: 1 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China. 2 Joint Institute of Virology (STU-HKU), Shantou University, Shantou, 515041, China; State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong SAR, China. 3 Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK. 4 Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. 5 Joint Institute of Virology (STU-HKU), Shantou University, Shantou, 515041, China. 6 Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330000, China. 7 Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China. 8 Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, 75015 Paris, France. 9 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 10 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China. Electronic address: yhj@fudan.edu.cn.

 

Abstract

OBJECTIVES:

The long-term dynamics of antibody responses in patients with influenza A(H7N9) virus infection are not well understood.

METHODS:

We conducted a longitudinal serological follow-up study in patients who were hospitalized with A(H7N9) virus infection, during 2013-2018. A(H7N9) virus-specific antibody responses were assessed by hemagglutination inhibition (HAI) and neutralization (NT) assays. A random intercept model was used to fit a curve to HAI antibody responses over time. HAI antibody responses were compared by clinical severity.

RESULTS:

Of 67 patients with A(H7N9) virus infection, HAI antibody titers reached 40 on average 11 days after illness onset and peaked at a titer of 290 after three months, and average titers of ≥80 and ≥40 were present until 11 months and 22 months respectively. HAI antibody responses were significantly higher in patients who experienced severe disease, including respiratory failure and acute respiratory distress syndrome, compared with patients who experienced less severe illness.

CONCLUSIONS:

Patients with A(H7N9) virus infection who survived severe disease mounted higher antibody responses that persisted for longer periods compared with those that experienced moderate disease. Studies of convalescent plasma treatment for A(H7N9) patients should consider collection of donor plasma from survivors of severe disease between 1-11 months after illness onset.

Copyright © 2020 Elsevier Ltd. All rights reserved.

KEYWORDS: Antibody response; Clinical severity; Follow-up; Influenza A(H7N9)

PMID: 31954742 DOI: 10.1016/j.jinf.2019.11.024

Keywords: Avian Influenza; H7N9; Serotherapy; Human.

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#Reassortment and #adaptive #mutations of an emerging #avian #influenza virus #H7N4 subtype in #China (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Reassortment and adaptive mutations of an emerging avian influenza virus H7N4 subtype in China

Bingqian Qu , Xue Li , Carol J. Cardona, Zheng Xing

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Published: January 17, 2020 / DOI: https://doi.org/10.1371/journal.pone.0227597

 

Abstract

Human infections with avian influenza viruses including H5, H7 and H9 hemagglutinin subtypes occur at a low rate. Among human infections with H7 viruses, regional outbreaks with H7N2, H7N3, H7N7 and H7N9 have been documented. Early in 2018, a human infection with a novel H7N4 avian influenza virus was reported in Jiangsu, China. This study is aimed at understanding the probable origin and molecular features of this emerging H7N4 virus. Genomic segments encoding hemagglutinin (HA) and neuraminidase (NA) of H7Nx and HxN4 viruses were compared with this H7N4 strain by alignment and phylogenetic tree analysis. Phylogenetic analysis indicated that the human H7N4 virus probably originated from multiple reassortments of avian H7N7 and H8N4 viruses for its HA and NA, respectively, and likely a regional uncharacterized virus for its internal segments. Our data excluded that circulating avian H9N2 viruses were the origin of the H7N4 internal segments, unlike the human H5N1 and H7N9 viruses that both had H9N2 backbones. This index case provided a unique opportunity to examine viral mutations by directly comparing the human isolate with its closest viral relatives isolated from avian species from the patient’s farm, which may suggest critical mutations required for viral adaptation in humans. Whole-genome scanning was performed and the sequences of the human and related avian H7N4 isolates were compared. Mutations in PB2 (E627K), PB2 (K683T), PB1-F2 (N47S), HA (N283D), HA(K321E), NA(A137V), NA(K296R) and M2 (C19Y) were identified in the human isolate while no mutations were found in PB1, NP, NS1, and NS2 of the human H7N4 compared to the avian H7N4 viruses. Our data in this report provide further evidence for the genesis of this novel H7N4 virus with a multi-reassortment model and show molecular changes that might be responsible for the transmission of this virus from chickens or ducks to and subsequent replication in humans.

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Citation: Qu B, Li X, Cardona CJ, Xing Z (2020) Reassortment and adaptive mutations of an emerging avian influenza virus H7N4 subtype in China. PLoS ONE 15(1): e0227597. https://doi.org/10.1371/journal.pone.0227597

Editor: Florian Krammer, Icahn School of Medicine at Mount Sinai, UNITED STATES

Received: August 26, 2019; Accepted: December 23, 2019; Published: January 17, 2020

Copyright: © 2020 Qu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript

Funding: ZX; National Natural Science Foundation of China; Grant No. 81571993; www.nsfc.gov.cn/; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Avian Influenza; H7N4; H7N7; H8N4; Reassortant strain; Human; China.

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Quantifying within-host #diversity of #H5N1 #influenza viruses in #humans and #poultry in #Cambodia (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

Louise H. Moncla , Trevor Bedford, Philippe Dussart, Srey Viseth Horm, Sareth Rith, Philippe Buchy, Erik A. Karlsson, Lifeng Li, Yongmei Liu, Huachen Zhu, Yi Guan, Thomas C. Friedrich, Paul F. Horwood

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Published: January 17, 2020 / DOI: https://doi.org/10.1371/journal.ppat.1008191 / This is an uncorrected proof.

 

Abstract

Avian influenza viruses (AIVs) periodically cross species barriers and infect humans. The likelihood that an AIV will evolve mammalian transmissibility depends on acquiring and selecting mutations during spillover, but data from natural infection is limited. We analyze deep sequencing data from infected humans and domestic ducks in Cambodia to examine how H5N1 viruses evolve during spillover. Overall, viral populations in both species are predominated by low-frequency (<10%) variation shaped by purifying selection and genetic drift, and half of the variants detected within-host are never detected on the H5N1 virus phylogeny. However, we do detect a subset of mutations linked to human receptor binding and replication (PB2 E627K, HA A150V, and HA Q238L) that arose in multiple, independent humans. PB2 E627K and HA A150V were also enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adaptive. Our data show that H5N1 viruses generate putative human-adapting mutations during natural spillover infection, many of which are detected at >5% frequency within-host. However, short infection times, genetic drift, and purifying selection likely restrict their ability to evolve extensively during a single infection. Applying evolutionary methods to sequence data, we reveal a detailed view of H5N1 virus adaptive potential, and develop a foundation for studying host-adaptation in other zoonotic viruses.

 

Author summary

H5N1 avian influenza viruses can cross species barriers and cause severe disease in humans. H5N1 viruses currently cannot replicate and transmit efficiently among humans, but animal infection studies and modeling experiments have suggested that human adaptation may require only a few mutations. However, data from natural spillover infection has been limited, posing a challenge for risk assessment. Here, we analyze a unique dataset of deep sequence data from H5N1 virus-infected humans and domestic ducks in Cambodia. We find that well-known markers of human receptor binding and replication arise in multiple, independent humans. We also find that 3 mutations detected within-host are enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adapting. However, we also show that within-host evolution in both humans and ducks are shaped heavily by purifying selection and genetic drift, and that a large fraction of within-host variation is never detected on the H5N1 phylogeny. Taken together, our data show that H5N1 viruses do generate human-adapting mutations during natural infection. However, short infection times, purifying selection, and genetic drift may severely limit how much H5N1 viruses can evolve during the course of a single infection.

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Citation: Moncla LH, Bedford T, Dussart P, Horm SV, Rith S, Buchy P, et al. (2020) Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia. PLoS Pathog 16(1): e1008191. https://doi.org/10.1371/journal.ppat.1008191

Editor: Wendy S. Barclay, Imperial College London, UNITED KINGDOM

Received: July 8, 2019; Accepted: November 4, 2019; Published: January 17, 2020

Copyright: © 2020 Moncla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All raw sequence data are available in the SRA under accession number PRJNA547644 (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA547644). All code used to analyze the data, as well as data files with within-host variant calls and phylogenetic trees are available at https://github.com/blab/h5n1-cambodia.

Funding: The study was funded by the US Agency for International Development (grant No. AID-442-G-14-00005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: Dr. Philippe Buchy is a former Head of Virology at Institut Pasteur du Cambodge and is currently an employee of GSK Vaccines, Singapore. The other authors declare no conflict of interest.

Keywords: Avian Influenza, H5N1, Human, Poultry, Cambodia.

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#Human #infection with a novel #reassortant #Eurasian-avian lineage #swine #H1N1 virus in northern #China (Emerg Microbes Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Emerg Microbes Infect. 2019;8(1):1535-1545. doi: 10.1080/22221751.2019.1679611.

Human infection with a novel reassortant Eurasian-avian lineage swine H1N1 virus in northern China.

Li X1, Guo L1, Liu C2, Cheng Y3, Kong M1, Yang L3, Zhuang Z1, Liu J3, Zou M1, Dong X1, Su X1, Gu Q1.

Author information: 1 Tianjin Centers for Disease Control and Prevention, Tianjin, People’s Republic of China. 2 Jizhou District Center for Disease Control and Prevention, Tianjin, People’s Republic of China. 3 Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China.

 

Abstract

Influenza A virus infections occur in different species, causing mild to severe respiratory symptoms that lead to a heavy disease burden. Eurasian avian-like swine influenza A(H1N1) viruses (EAS-H1N1) are predominant in pigs and occasionally infect humans. An influenza A(H1N1) virus was isolated from a boy who was suffering from fever and headache and designated as A/Tianjin-baodi/1606/2018(H1N1). Full-genome sequencing and phylogenetic analysis revealed that A/Tianjin-baodi/1606/2018(H1N1) is a novel reassortant EAS-H1N1 containing gene segments from EAS-H1N1 (HA and NA), classical swine H1N1(NS) and A(H1N1)pdm09(PB2, PB2, PA, NP and M) viruses. The isolation and analysis of A/Tianjin-baodi/1606/2018(H1) provide further evidence that EAS-H1N1 poses a threat to human health and greater attention should be paid to surveillance of influenza virus infection in pigs and humans.

KEYWORDS: EAS-H1N1; Influenza A virus; Phylogenetic analysis; molecular characteristics; triple-reassortant

PMID: 31661383 PMCID: PMC6830285 DOI: 10.1080/22221751.2019.1679611 [Indexed for MEDLINE] Free PMC Article

Keywords: Influenza A; Swine Influenza; H1N1; H1N1pdm09; Reassortant strain; Human; China.

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#Human-infecting #influenza A (#H9N2) virus: A forgotten potential #pandemic strain? (Zoonoses Public Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Zoonoses Public Health. 2020 Jan 12. doi: 10.1111/zph.12685. [Epub ahead of print]

Human-infecting influenza A (H9N2) virus: A forgotten potential pandemic strain?

Song W1,2, Qin K3.

Author information: 1 State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou, China. 2 Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China. 3 National Institute of Viral Disease Control and Prevention, China CDC, Beijing, China.

 

Abstract

Continuously emergence of human infection with avian influenza A virus poses persistent threat to human health, as illustrated in H5N1, H7N9 and recent surge of H9N2 infections. Long-term prevalence of H9N2 avian influenza A virus in China and adjacent regions favours the interspecies transmissions from avian to human. Establishment of multiple genotypes of H9N2 variants in this region contributes to the emergence of novel H7N9 and H10N8 viruses which caused human fatalities. Recent increasing human infection with H9N2 virus in China highlights the necessity to closely monitor the interspecies transmission events. Available human H9N2 sequences revealed that Y280/G9 lineage was responsible for the most of human cases. Presence of adaptive mutations beyond the human-like receptor binding was indicative of the capacity of readily infecting new hosts without prior adaptation. Moreover, enlarged host range of H9N2 virus in this region substantially increased the transmission among mammals. Meanwhile, serological surveys implied human was more susceptible to H9N2 infection, compared with panzootic H5 and H7 subtype avian influenza virus. Thus, control at the source will be the ultimate and effective option for H9N2 pandemic preparedness. This review comprehensively summarized recent updates on H9N2 human infections, aiming to shed light on the prevention strategies against this strain with pandemic potential.

© 2020 Blackwell Verlag GmbH.

KEYWORDS: H9N2; influenza; pandemic

PMID: 31930694 DOI: 10.1111/zph.12685

Keywords: Avian Influenza; H9N2; Pandemic Preparedness.

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Association Between #Cardiac #Injury and #Mortality in Hospitalized Patients Infected With #Avian #Influenza A (#H7N9) Virus (Crit Care Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Crit Care Med. 2020 Jan 9. doi: 10.1097/CCM.0000000000004207. [Epub ahead of print]

Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus.

Gao C1,2, Wang Y3, Gu X4,5, Shen X6, Zhou D7, Zhou S8, Huang JA9, Cao B3,5,10, Guo Q2; for the Community-Acquired Pneumonia–China Network.

Author information: 1 Department of Critical Care Medicine, Dushuhu Public Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China. 2 Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. 3 Department of Pulmonary and Critical Care Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, China. 4 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China. 5 Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China. 6 Department of Critical Care Medicine, The Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, China. 7 Department of infectious diseases, Taizhou People’s Hospital, Taizhou, Jiangsu, China. 8 Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, China. 9 Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. 10 Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.

 

Abstract

OBJECTIVES:

To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus.

DESIGN:

Retrospective cohort study.

SETTING:

A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus-infected patients between January 22, 2015, and June 16, 2017.

PATIENTS:

A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower PaO2/FIO2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31-3.24) during hospitalization.

CONCLUSIONS:

Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.

PMID: 31923027 DOI: 10.1097/CCM.0000000000004207

Keywords: Avian Influenza; H7N9; Human; Cardiology.

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