#Evolution of highly pathogenic #H7N3 #avian #influenza viruses in #Mexico (Zoonoses Public Health, abstract)

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

Zoonoses Public Health. 2020 Jan 7. doi: 10.1111/zph.12673. [Epub ahead of print]

Evolution of highly pathogenic H7N3 avian influenza viruses in Mexico.

Trovão NS1, Talavera GA2, Nelson MI1, Perez de la Rosa JD3.

Author information: 1 Fogarty International Center, National Institutes of Health, Bethesda, Maryland. 2 Universidad Autónoma de Yucatán, Yucatán, Mexico. 3 Centro Nacional de Servicios de Constatación en Salud Animal (CENAPA), Morelos, Mexico.

 

Abstract

Highly pathogenic H7N3 influenza A viruses have persisted in poultry in Mexico since 2012, diversifying into multiple lineages that have spread to three Mexican states, as of 2016. The H7N3 viruses segregate into three distinct clades that are geographically structured. All 2016 viruses are resistant to adamantane antiviral drugs and have an extended 24-nucleotide insertion at the HA cleavage site that was acquired from host 28S ribosomal RNA.

Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

KEYWORDS: BEAST; H7N3; H7N3 subtype; avian influenza virus; evolutionary dynamics; influenza in birds; phylogenetics

PMID: 31912652 DOI: 10.1111/zph.12673

Keywords: Avian Influenza; H7N3; Poultry; Mexico; Antivirals; Drugs Resistance; Amantadine.

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The #evolution and #genetic #diversity of #avian #influenza A(#H9N2) viruses in #Cambodia, 2015 – 2016 (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 – 2016

Annika Suttie, Songha Tok, Sokhoun Yann, Ponnarath Keo, Srey Viseth Horm, Merryn Roe, Matthew Kaye, San Sorn, Davun Holl, Sothyra Tum, Ian G. Barr, Aeron C. Hurt, Andrew R. Greenhill,  [ … ], Paul F. Horwood

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Published: December 9, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225428

 

Abstract

Low pathogenic A(H9N2) subtype avian influenza viruses (AIVs) were originally detected in Cambodian poultry in 2013, and now circulate endemically. We sequenced and characterised 64 A(H9N2) AIVs detected in Cambodian poultry (chickens and ducks) from January 2015 to May 2016. All A(H9) viruses collected in 2015 and 2016 belonged to a new BJ/94-like h9-4.2.5 sub-lineage that emerged in the region during or after 2013, and was distinct to previously detected Cambodian viruses. Overall, there was a reduction of genetic diversity of H9N2 since 2013, however two genotypes were detected in circulation, P and V, with extensive reassortment between the viruses. Phylogenetic analysis showed a close relationship between A(H9N2) AIVs detected in Cambodian and Vietnamese poultry, highlighting cross-border trade/movement of live, domestic poultry between the countries. Wild birds may also play a role in A(H9N2) transmission in the region. Some genes of the Cambodian isolates frequently clustered with zoonotic A(H7N9), A(H9N2) and A(H10N8) viruses, suggesting a common ecology. Molecular analysis showed 100% of viruses contained the hemagglutinin (HA) Q226L substitution, which favours mammalian receptor type binding. All viruses were susceptible to the neuraminidase inhibitor antivirals; however, 41% contained the matrix (M2) S31N substitution associated with resistance to adamantanes. Overall, Cambodian A(H9N2) viruses possessed factors known to increase zoonotic potential, and therefore their evolution should be continually monitored.

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Citation: Suttie A, Tok S, Yann S, Keo P, Horm SV, Roe M, et al. (2019) The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 – 2016. PLoS ONE 14(12): e0225428. https://doi.org/10.1371/journal.pone.0225428

Editor: Charles J. Russell, St. Jude Children’s Research Hospital, UNITED STATES

Received: August 28, 2019; Accepted: November 4, 2019; Published: December 9, 2019

Copyright: © 2019 Suttie 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 and its Supporting Information files.

Funding: This publication is the result of work conducted under a cooperative agreement with the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (HHS), grant number IDSEP140020-01-00 (PH). The study was also funded, in part, by the US Agency for International Development (grant No. AID-442-G-14-00005) (PH). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health (IB). 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; H9N2; H7N9; H9N2; H10N8; Reassortant strain; Cambodia; Antivirals; Drugs Resistance; Amantadine; Oseltamivir; Zanamivir.

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#Diversity of A(#H5N1) clade 2.3.2.1c #avian #influenza viruses with evidence of #reassortment in #Cambodia, 2014-2016 (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Diversity of A(H5N1) clade 2.3.2.1c avian influenza viruses with evidence of reassortment in Cambodia, 2014-2016

Annika Suttie,  Songha Tok, Sokhoun Yann, Ponnarath Keo, Srey Viseth Horm, Merryn Roe, Matthew Kaye, San Sorn, Davun Holl, Sothyra Tum, Philippe Buchy, Ian Barr, Aeron Hurt,  [ … ], Paul F. Horwood

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Published: December 9, 2019 / DOI: https://doi.org/10.1371/journal.pone.0226108

 

Abstract

In Cambodia, highly pathogenic avian influenza A(H5N1) subtype viruses circulate endemically causing poultry outbreaks and zoonotic human cases. To investigate the genomic diversity and development of endemicity of the predominantly circulating clade 2.3.2.1c A(H5N1) viruses, we characterised 68 AIVs detected in poultry, the environment and from a single human A(H5N1) case from January 2014 to December 2016. Full genomes were generated for 42 A(H5N1) viruses. Phylogenetic analysis shows that five clade 2.3.2.1c genotypes, designated KH1 to KH5, were circulating in Cambodia during this period. The genotypes arose through multiple reassortment events with the neuraminidase (NA) and internal genes belonging to H5N1 clade 2.3.2.1a, clade 2.3.2.1b or A(H9N2) lineages. Phylogenies suggest that the Cambodian AIVs were derived from viruses circulating between Cambodian and Vietnamese poultry. Molecular analyses show that these viruses contained the hemagglutinin (HA) gene substitutions D94N, S133A, S155N, T156A, T188I and K189R known to increase binding to the human-type α2,6-linked sialic acid receptors. Two A(H5N1) viruses displayed the M2 gene S31N or A30T substitutions indicative of adamantane resistance, however, susceptibility testing towards neuraminidase inhibitors (oseltamivir, zanamivir, lananmivir and peramivir) of a subset of thirty clade 2.3.2.1c viruses showed susceptibility to all four drugs. This study shows that A(H5N1) viruses continue to reassort with other A(H5N1) and A(H9N2) viruses that are endemic in the region, highlighting the risk of introduction and emergence of novel A(H5N1) genotypes in Cambodia.

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Citation: Suttie A, Tok S, Yann S, Keo P, Horm SV, Roe M, et al. (2019) Diversity of A(H5N1) clade 2.3.2.1c avian influenza viruses with evidence of reassortment in Cambodia, 2014-2016. PLoS ONE 14(12): e0226108. https://doi.org/10.1371/journal.pone.0226108

Editor: Charles J. Russell, St. Jude Children’s Research Hospital, UNITED STATES

Received: August 7, 2019; Accepted: November 18, 2019; Published: December 9, 2019

Copyright: © 2019 Suttie 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 and its Supporting Information files.

Funding: This publication is the result of work conducted under a cooperative agreement with the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (HHS), grant number IDSEP140020-01-00. Its contents and conclusions are solely the responsibility of the authors and do not represent the official views of HHS. The study was also funded, in part, by the US Agency for International Development (grant No. AID-442-G-14-00005) and partially funded through the UK Research and Innovation Global Challenges Research Fund to The Consortium of Animal Market Networks to Assess Risk of Emerging Infectious Diseases Through Enhanced Surveillance (CANARIES; grant No. GCRFNGR3\1497). Annika Suttie is funded by an Australian Government Research Training Program Scholarship and a Faculty of Science and Technology Research Scholarship from Federation University. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. GlaxoSmithKline Biologicals SA provided support in the form of salary for an author [PB], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. The authors are solely responsible for final content and interpretation.

Competing interests: GlaxoSmithKline Biologicals SA provided support in the form of salary for an author [PB]. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Keywords: Avian Influenza; H5N1; H9N2; Reassortant strains; Poultry; Human; Antivirals; Drugs Resistance; Amantadine; Oseltamivir; Zanamivir; Cambodia.

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#Genotypic #evolution and #epidemiological characteristics of #H9N2 #influenza virus in #Shandong Province, #China (Poult Sci., abstract)

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

Poult Sci. 2019 Sep 1;98(9):3488-3495. doi: 10.3382/ps/pez151.

Genotypic evolution and epidemiological characteristics of H9N2 influenza virus in Shandong Province, China.

Li Y1, Liu M1, Sun Q1, Zhang H1, Zhang H1, Jiang S1, Liu S1, Huang Y2.

Author information: 1 College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian 271018, China. 2 Shandong Key Laboratory of Animal Disease Control and Breeding, Animal Husbandry and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China.

 

Abstract

H9N2 avian influenza has been prevalent in chicken flocks of China for years. In the first half year of 2018, clinical cases of suspected H9N2 infection were collected from chicken flocks in Shandong province. Nine strains of H9N2 influenza virus were isolated. The pathological changes of the dead chickens were mainly respiratory inflammation, renal swelling, and secondary infection. The microscopic lesions were consistent with the pathogenic characteristics of H9N2 influenza virus. From November 2017 to June 2018, a total of 3,380 serum samples were randomly collected from commercial laying hens in Shandong Province. The H9 antibody levels were tested with the isolated strain (CK/SD/231/17) as the antigen. It showed that the average of antibody titers of H9 avian influenza was 9.24 1og2. Hemagglutination inhibition experiments were conducted on chicken serum with the vaccine virus and the isolated virus (CK/SD/231/17) as the antigens. It was found that the antibody titer measured with the vaccine virus was 1 or 2 titers higher than the isolated strain. It indicated that the antigenicity of H9N2 circulating strain was different from that of vaccine strain. The nucleotide sequences of HA gene of these recent H9N2 avian influenza virus isolates shared homologies from 93.8 to 99.9%. Phylogenetic analysis revealed that the eight gene segments of the viruses were in the same clades with G57 gene reference strain. The amino acid site analysis of influenza resistance showed that the virus was sensitive to neuraminidase inhibitors and resistant to amantadine.

Highlights:

The protection rate of the H9N2 AIV vaccine almost reached 100% before 2016, but the antibody level of serum samples showed high diversity in this study, which means the poultry were infected. The antigenicity of isolated H9N2 strains was different from that of vaccine strain. Current available vaccines may provide only limited protection.

© 2019 Poultry Science Association Inc.

KEYWORDS: CK/GD/SS/94; CK/SH/F/98; H9N2 subtype; Shandong; avian influenza

PMID: 30941436 DOI: 10.3382/ps/pez151 [Indexed for MEDLINE]

Keywords: Avian Influenza; H9N2; Poultry; Vaccines; Antivirals; Drugs Resistance; Oseltamivir; Amantadine; Shandong; China.

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A study of the #relationship between #human #infection with #avian #influenza a (#H5N6) and environmental avian influenza viruses in #Fujian, #China (BMC Infect Dis., abstract)

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

BMC Infect Dis. 2019 Sep 2;19(1):762. doi: 10.1186/s12879-019-4145-6.

A study of the relationship between human infection with avian influenza a (H5N6) and environmental avian influenza viruses in Fujian, China.

Chen P1, Xie JF1,2, Lin Q2, Zhao L2, Zhang YH2, Chen HB2, Weng YW1,2, Huang Z2, Zheng KC3,4.

Author information: 1 College of Public Health, Fujian Medical University, No. 88, Jiaotong Road, Taijiang District, Fuzhou, 350000, China. 2 Fujian Center for Disease Control and Prevention, Fujian Provincial Key Laboratory of Zoonosis Research, Fuzhou, 350001, China. 3 College of Public Health, Fujian Medical University, No. 88, Jiaotong Road, Taijiang District, Fuzhou, 350000, China. kingdadi9909@126.com. 4 Fujian Center for Disease Control and Prevention, Fujian Provincial Key Laboratory of Zoonosis Research, Fuzhou, 350001, China. kingdadi9909@126.com.

 

Abstract

BACKGROUND:

Avian influenza A (H5N6) virus poses a great threat to the human health since it is capable to cross the species barrier and infect humans. Although human infections are believed to largely originate from poultry contaminations, the transmissibility is unclear and only limited information was available on poultry environment contaminations, especially in Fujian Province.

METHODS:

A total of 4901 environmental samples were collected and tested for Avian Influenza Virus (AIV) from six cities in Fujian Province through the Fujian Influenza Surveillance System from 2013 to 2017. Two patient-related samples were taken from Fujian’s first confirmed H5N6 human case and his backyard chicken feces in 2017. Chi-square test or Fisher’s exact probability test was used to compare the AIV and the viral subtype positive rates among samples from different Surveillance cities, surveillance sites, sample types, and seasons. Phylogenetic tree analysis and molecular analysis were conducted to track the viral transmission route of the human infection and to map out the evolutions of H5N6 in Fujian.

RESULTS:

The overall positive rate of the H5 subtype AIVs was 4.24% (208/4903). There were distinctive differences (p < 0.05) in the positive rates in samples from different cities, sample sites, sample types and seasons. The viruses from the patient and his backyard chicken feces shared high homologies (99.9-100%) in all the eight gene segments. Phylogenetic trees also showed that these two H5N6 viruses were closely related to each other, and were classified into the same genetic clade 2.3.4.4 with another six H5N6 isolates from the environmental samples. The patient’s H5N6 virus carried genes from H6N6, H5N8 and H5N6 viruses originated from different areas. The R294K or N294S substitution was not detected in the neuraminidase (NA). The S31 N substitution in the matrix2 (M2) gene was detected but only in one strain from the environmental samples.

CONCLUSIONS:

The H5 subtype of AIVs has started circulating in the poultry environments in Fujian Province. The patient’s viral strain originated from the chicken feces in his backyard. Genetic reassortment in H5N6 viruses in Fujian Province was indicated. The H5N6 viruses currently circulating in Fujian Province were still commonly sensitive to Oseltamivir and Zanamivir, but the resistance against Amantadine has emerged.

KEYWORDS: Avian influenza a (H5N6) virus; Environmental contamination; Phylogenetic analysis

PMID: 31477028 DOI: 10.1186/s12879-019-4145-6

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Amantadine; H5N6; H6N6; H5N8; Reassortant strain; Avian Influenza; Human; Fujian; China.

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The effect of #amantadine on an ion channel protein from #Chikungunya virus (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

The effect of amantadine on an ion channel protein from Chikungunya virus

Debajit Dey, Shumaila Iqbal Siddiqui, Prabhudutta Mamidi, Sukanya Ghosh, Chandra Shekhar Kumar, Soma Chattopadhyay, Subhendu Ghosh, Manidipa Banerjee

Published: July 24, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007548

 

Abstract

Viroporins like influenza A virus M2, hepatitis C virus p7, HIV-1 Vpu and picornavirus 2B associate with host membranes, and create hydrophilic corridors, which are critical for viral entry, replication and egress. The 6K proteins from alphaviruses are conjectured to be viroporins, essential during egress of progeny viruses from host membranes, although the analogue in Chikungunya Virus (CHIKV) remains relatively uncharacterized. Using a combination of electrophysiology, confocal and electron microscopy, and molecular dynamics simulations we show for the first time that CHIKV 6K is an ion channel forming protein that primarily associates with endoplasmic reticulum (ER) membranes. The ion channel activity of 6K can be inhibited by amantadine, an antiviral developed against the M2 protein of Influenza A virus; and CHIKV infection of cultured cells can be effectively inhibited in presence of this drug. Our study provides crucial mechanistic insights into the functionality of 6K during CHIKV-host interaction and suggests that 6K is a potential therapeutic drug target, with amantadine and its derivatives being strong candidates for further development.

 

Author summary

Chikungunya fever is a severe crippling illness caused by the arthropod-borne virus CHIKV. Originally from the African subcontinent, the virus has now spread worldwide and is responsible for substantial morbidity and economic loss. The existing treatment against CHIKV is primarily symptomatic, and it is imperative that specific therapeutics be devised. The present study provides detailed insight into the functionality of 6K, an ion channel forming protein of CHIKV. Amantadine, a known antiviral against influenza virus, also inhibits CHIKV replication in cell culture and drastically alters the morphology of virus particles. This work highlights striking parallels among functionalities of virus-encoded membrane-interacting proteins, which may be exploited for developing broad-spectrum antivirals.

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Citation: Dey D, Siddiqui SI, Mamidi P, Ghosh S, Kumar CS, Chattopadhyay S, et al. (2019) The effect of amantadine on an ion channel protein from Chikungunya virus. PLoS Negl Trop Dis 13(7): e0007548. https://doi.org/10.1371/journal.pntd.0007548

Editor: Abdallah M. Samy, Faculty of Science, Ain Shams University (ASU), EGYPT

Received: December 27, 2018; Accepted: June 11, 2019; Published: July 24, 2019

Copyright: © 2019 Dey 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 and its Supporting Information files.

Funding: Funding was secured by MB (BT/PR29264/BRB/10/1710/2018) from Department of Biotechnology (DBT) India (http://www.dbtindia.nic.in). However, DBT had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript. DD thanks CSIR for research fellowship (09/086(1183)/2013-EMR-I).

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

Keywords: Antivirals; Amantadine; Chikungunya fever.

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#Viral #Factors Associated With the High #Mortality Related to #Human #Infections With Clade 2.1 #Influenza A/ #H5N1 Virus in #Indonesia (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2019 Apr 26. pii: ciz328. doi: 10.1093/cid/ciz328. [Epub ahead of print]

Viral Factors Associated With the High Mortality Related to Human Infections With Clade 2.1 Influenza A/H5N1 Virus in Indonesia.

Pawestri HA1, Eggink D2, Isfandari S1, Thanh TT3,4, Rogier van Doorn H3,5, Setiawaty V1, de Jong MD2.

Author information: 1 National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia. 2 Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands. 3 Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. 4 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. 5 Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom.

 

Abstract

BACKGROUND:

Since their emergence in Indonesia in 2005, 200 human infections with clade 2.1 highly pathogenic avian influenza A/H5N1 virus have been reported, associated with exceptionally high mortality (84%) compared to regions affected by other genetic clades of this virus. To provide potential clues towards understanding this high mortality, detailed clinical virological analyses were performed in specimens from 180 H5N1 patients, representing 90% of all Indonesian patients and 20% of reported H5N1-infected patients globally.

METHODS:

H5N1 RNA was quantified in available upper- and lower-respiratory tract specimens as well as fecal and blood samples from 180 patients with confirmed infection between 2005 and 2017. Mutations in the neuraminidase and M2 genes that confer resistance to oseltamivir and adamantanes were assessed. Fatal and nonfatal cases were compared.

RESULTS:

High viral RNA loads in nasal and pharyngeal specimens were associated with fatal outcome. Mortality increased over time during the study period, which correlated with increasing viral RNA loads on admission. Furthermore, the prevalence of amantadine resistance-conferring M2 mutations increased over time, and viral loads were higher in patients infected with viruses that harbored these mutations. Compared to observations from other regions, viral RNA was detected more frequently in feces (80%) and particularly in blood (85%), and antiviral responses to oseltamivir appeared less pronounced.

CONCLUSIONS:

These observations confirm the association of viral load with outcome of human H5N1 infections and suggest potential differences in virulence and antiviral responses to oseltamivir that may explain the exceptionally high mortality related to clade 2.1 H5N1 infections in Indonesia.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: H5N1; highly pathogenic avian influenza virus; mortality; resistance; viral load

PMID: 31321436 DOI: 10.1093/cid/ciz328

Keywords: Avian Influenza; H5N1; Human; Antivirals, Drugs Resistance; Amantadine; Oseltamivir.

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