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

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PLoS One. 2019 Dec 9;14(12):e0226108. doi: 10.1371/journal.pone.0226108. eCollection 2019. Diversity of A(H5N1) clade 2.3.2.1c avian influenza viruses with evidence of reassortment in Cambodia, 2014-2016.

Suttie A^1,2,3, Tok S¹, Yann S¹, Keo P¹, Horm SV¹, Roe M³, Kaye M³, Sorn S⁴, Holl D⁴, Tum S⁴, Buchy P^1,5, Barr I³, Hurt A³, Greenhill AR², Karlsson EA¹, Vijaykrishna D⁶, Deng YM³, Dussart P¹, Horwood PF^1,7.
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1 Virology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, Cambodia. 2 School of Health and Life Sciences, Federation University, Churchill, Australia. 3 WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 4 National Animal Health and Production Research Institute, General Directorate of Animal Health and Production, Cambodian Ministry of Agriculture, Forestry and Fisheries, Phnom Penh, Cambodia. 5 GlaxoSmithKline Vaccines R&D Intercontinental, Singapore, Singapore. 6 Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia. 7 College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia.

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.


PMID: 31815962 DOI: 10.1371/journal.pone.0226108
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