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

Abstract

H5N6 avian influenza virus (AIV) has posed a potential threat to public health since its emergence in China in 2013. To understand the evolution and emergence of H5N6 AIV in the avian population, we performed molecular surveillance of live poultry markets (LPMs) in Wugang Prefecture, Hunan Province, in central China, during 2014 and 2015. Wugang Prefecture is located on the Eastern Asian-Australian migratory bird flyway, and a human death due to an H5N6 virus was reported in the prefecture on 21 November 2016. In total, we sampled and sequenced the complete genomes of 175 H5N6 AIVs. Notably, our analysis revealed that H5N6 AIVs contain at least six genotypes arising from segment reassortment, including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2 and a novel NP gene that has its origins with H7N3 viruses. In addition, phylogenetic analysis revealed that genetically similar H5N6 AIVs tend to cluster according to their geographic regions of origin. These results help to reveal the evolutionary behavior of influenza viruses prior to their emergence in humans.IMPORTANCE The newly emerged H5N6 influenza A virus has caused more than 10 human deaths in China since 2013. In November 2016, a human death due to an H5N6 virus, in Wugang Prefecture, Hunan Province, was confirmed by the WHO. To better understand the evolution and emergence of H5N6 viruses, we surveyed live poultry markets (LPMs) in Wugang Prefecture before the reported human death, with a focus on revealing the diversity and genomic origins of H5N6 in birds during 2014 and 2015. In general, H5N6 viruses in this region were most closely related to H5N1 clade 2.3.4.4, with the exception of one virus with an HA gene derived from clade 2.3.2 such that it represents a novel reassortant. Clearly, the ongoing surveillance of LPMs is central to monitoring the emergence of pathogenic influenza viruses.

Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes

“…The N6 subtype of influenza viruses, in combination with highly pathogenic (HP) AIVs of the H5 subtype, have been recently reported to infect humans in China (16,23). Although there have been no recent reports of NAI resistance in the N6 subtype (24), the fatality risk of A(H5N6) human cases has been found to be similar to or higher than those of HPAI A(H5N1) and A(H7N9) infections (17). To study the N6 AIV subtype, we used A/EM/Korea/W20/2005 (H4N6) virus and generated a random mutant virus library in the background of PR8 virus (7ϩ1).…”

Respiratory viral infections

“…The genetic and antigenic evolution of error prone RNA respiratory viruses, particularly influenza, has been of interest for several decades [37,38]. Understanding the selective pressure exerted by pre-existing immunity on viral evolution may help design more effective influenza vaccines and surveillance of animal populations can be critical for early identification of emerging influenza viruses [39]. Advances in deep sequencing make it possible to measure low frequency within host viral diversity and factors such as antigenic diversity, antiviral resistance, and tissue specificity can now be studied to understand the complexities of viral evolution [40].…”

Avian influenza overview September – November 2017

“…Province provided evidence for the existence of at least six genotypes arising from segment reassortment, including a variant that possessed an HA from A(H5N1) clade 2.3.2 (Du et al, 2017).…”