[Source: PLOS One, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Diversity of A(H5N1) clade 18.104.22.168c 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
Published: December 9, 2019 / DOI: https://doi.org/10.1371/journal.pone.0226108
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 22.214.171.124c 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 126.96.36.199c 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 188.8.131.52a, clade 184.108.40.206b 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 220.127.116.11c 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.
Citation: Suttie A, Tok S, Yann S, Keo P, Horm SV, Roe M, et al. (2019) Diversity of A(H5N1) clade 18.104.22.168c 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.