Novel avian influenza A (H5N6) viruses isolated in migratory waterfowl before the first human case reported in China, 2014

Abstract

In May 2014, China formally confirmed the first human infection with the novel H5N6 avian influenza virus (AIV) in Sichuan Province. Before the first human case was reported, surveillance of AIVs in wild birds resulted in the detection of three H5N6 viruses in faecal samples from migratory waterfowl in Chenhu wetlands, Hubei Province, China. Genetic and phylogenetic analyses revealed that these three novel viruses were closely related to the H5N6 virus that has caused human infections in China since 2014. A Bayesian phylogenetic reconstruction of all eight segments suggests multiple reassortment events in the evolution of these viruses. The hemagglutinin (HA) and neuraminidase (NA) originated from the H5N2 and H6N6 AIVs, respectively, whereas all six internal genes were derived from avian H5N1 viruses. The reassortant may have occurred in eastern China during 2012–2013. A phylogeographic analysis of the HA and NA genes traced the viruses to southern China, from where they spread to other areas via eastern China. A receptor-binding test showed that H5N6 viruses from migratory waterfowl had human-type receptor-binding activity, suggesting a potential for transmission to humans. These data suggest that migratory waterfowl may play a role in the dissemination of novel H5N6 viruses.

Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses

“…Previous studies revealed that the HPAI H5N6 virus contained the hemagglutinin (HA) gene of H5 clade 2.3.4.4, the internal genes of H5 clade 2.3.2.1, and the NA gene from the H6N6 avian virus (9,12,13). Based on the genetic evidence, HPAI H5N6 virus likely originated from migratory waterfowl (14). Further reassortment with other avian influenza viruses generated multiple genotypes of HPAI H5N6 viruses (15)(16)(17)(18)(19).…”

“…with lower but increased affinity for the human-like receptor (␣-2,6 sialic acid) (14,39,40). The mutations identified in human isolates (S123P, I151T, T156A, and the deletion at position 126 in HA) should be further investigated to identify their effects on the receptor binding preferences of H5N6 viruses.…”

Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China

“…Recently, with more H5N6 genomes sequenced, it has become clear that the gene segments of these viruses derived from a variety of AIV subtypes. Specifically, the PB2 gene of some H5N6 AIVs derived from that of H6N6 viruses, while the PB1 gene originated in H3 subtype viruses (9); a novel H5N6 virus isolated from migratory waterfowl possessed a hemagglutinin (HA) gene that was related to that of H5N2 viruses (10); the internal genes of viruses isolated from two human cases in 2015 derived from H7N9/H9N2 viruses in chickens (11); human infections in Guangdong Province, China, in 2015 were due to a newly emerged H5N6 virus that was a reassortant between H6N6 and H9N2 viruses (12); and a human-associated H5N6 (clade 2.3.3.4) virus sampled in China during 2014 to 2015 was a triple reassortant derived from H6N6, H5N1 (clade 2.3.1.1), and H5N6 (2.3.4.4) viruses (13). In addition, a recent study of multiple live poultry markets (LPMs) in southern China revealed that the HA gene of H5N6 viruses derived from clade 2.3.4.4, the NA gene derived from H6N6 viruses, and all six internal gene segments had their origins in clades 2.3.4.4 and 2.3.2.1 of H9N2/H7N9 viruses (14).…”

Avian influenza overview September – November 2017

“…Two types of A(H5N6) can be distinguished based on the length of NA: with-and without truncated NA stems (deletions at amino acid positions 59-69), a signature of adaptation to terrestrial poultry ( (Bi et al, 2016;Sun et al, 2016;Yang et al, 2017).…”