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.
Highlights
Avian influenza viruses (AIVs; family Orthomyxoviridae) continuously circulate globally in their natural reservoir, wild waterbirds (Orders Anseriformes and Charadriiformes)
During 2014–2016, 42 A(H5N1) clade 2.3.2.1c viruses were isolated from poultry (21 chickens and 21 ducks) in Cambodian live bird markets (LBMs) (S1 Table)
A(H5N1) highly pathogenic avian influenza (HPAI) viruses were introduced into Cambodia in 2004
Summary
Avian influenza viruses (AIVs; family Orthomyxoviridae) continuously circulate globally in their natural reservoir, wild waterbirds (Orders Anseriformes and Charadriiformes). The majority of AIVs circulate as low pathogenic avian influenza viruses that cause mild or no disease in domestic poultry [1,2]. Subtype A(H5) and A(H7) AIVs are capable of mutating to form highly pathogenic avian influenza (HPAI) viruses that can cause high morbidity and mortality in poultry flocks [3,4]. The A/goose/ Guangdong/1/1996 (Gs/Gd) A(H5N1) lineage has disseminated globally causing intermittent outbreaks in domestic poultry and sporadic human infections [6,7]. The primary risk factor for human infection with AIVs is close contact to poultry [9,10] and in vivo studies have shown that A(H5) viruses (with as few as five amino acid substitutions) can acquire aerosol transmissibility in ferrets [11,12]. Sustained transmission of A(H5) AIVs between humans has not been documented, though mutations enabling greater transmissibility among humans greatly increases the pandemic threat [13,14]
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