The Genomic Evolution and the Transmission Dynamics of H6N2 Avian Influenza A Viruses in Southern China

Abstract

In China, the broad prevalence of H6 subtype influenza viruses, increasingly detected in aquatic birds, promotes their exchange materials with other highly pathogenic human-infecting H5N1, H5N6, and H7N9 influenza viruses. Strikingly, some H6 subtype viruses can infect pigs, dogs, and humans, posing risks to public health. In this study, 9 H6N2 viruses recovered from waterfowl species in the Guangdong province of China in 2018 were isolated and sequenced. Phylogenetic analysis revealed that the genome sequences of these H6N2 viruses belonged to Group I, except for the NP gene in Group III. Coalescent analyses demonstrated that the reassortment of NA and NS genes have occurred in two independent clusters, suggesting H6 subtype viruses had been undergoing a complex reassortant. To examine the evolutionary dynamics and the dissemination of the H6 subtype viruses, a Bayesian stochastic search variable selection was performed for results showing higher viral migration rates between closer provinces, including Guangdong, Jiangxi, Guangxi, and Fujian. Notably, the transmission routes of the H6 subtype viruses were concentrated in Jiangxi Province, the most frequent location for input and output transmission and a region containing Poyang Lake, a well-known wintering site for migration birds. We also found that the aquatic birds, especially ducks, were the most common input source of the viral transmission. In addition, we also found that eight positively selected amino acid sites were identified in HA protein. Given their continuous dissemination and the broad prevalence of the H6 subtype influenza viruses, continued surveillance is warranted in the future.

Evolution and Reassortment of H6 Subtype Avian Influenza Viruses

“…Although early literature indicated that H6 AIV has barriers to interspecific transmission, transmission between domestic ducks and terrestrial poultry is uncommon [27]. However, the recent BSSVS procedure by Yuan Z et al showed that ducks were the main source for introducing H6 into chickens and geese [16]. Chickens and geese were also the main poultry infected with H6 AIV, accounting for 16% and 12%, respectively.…”

“…N1, N2, and N6 were the major H6 AIV subtypes in China, with duck derived H6N2 predominating from 2000–2005. After that, N2 and N6 replaced N1 subtypes as the main NA subtypes of H6-subtype AIVs in China, and the proportion of H6N6 subtypes has gradually increased since 2009 [ 13 , 16 ]. In China, the H6 subtype AIV is mainly concentrated in the southern region, with Guangdong Province having the largest number of isolated strains of 608 strains, followed by Hunan Province and Fujian Province.…”

“…The Eurasian genealogy is predominant and further divided into ST339-like, ST2853-like and HN57-like subbranches [ 27 ]. The ST339-like and ST2853-like branches of H6Nx are the two main prevalent branches in China [ 16 ].…”

“…Today, all H6 AIVs found have been LPAIV [ 13 ]. Despite H6 AIV being an LPAIV, A/teal/HK/W312/97 (H6N1) has been identified as a potential precursor of A/Hong Kong/156/1997 (H5N1) [ 14 ], and some of the H6NX strains have been identified as donors for H5 and H9N2 subtype AIV [ 15 , 16 ]. Such reassortments may pose a major threat to public health.…”

Avian H6 Influenza Viruses in Vietnamese Live Bird Markets during 2018–2021

“…Group II included H6N2 and H6N6 viruses from the Guangdong and Fujian provinces [ 9 ], whereas viruses in Group III came from Jiangxi, Hunan, and Guangxi and possessed Nas of different subtypes [ 9 ]. In later years, most of the analyzed Chinese H6 viruses belonged to Groups I and II, with an increasing percentage of viruses possessing an NA gene of the N6 subtype [ 10 , 11 , 12 , 13 ]. Moreover, analysis of recent Asian H6 viruses revealed frequent reassortment with other influenza A viruses, resulting in multiple genotypes that have been co-circulating [ 14 , 15 , 16 , 17 ].…”