Phylogenetic and Phylogeographic Analysis of the Highly Pathogenic H5N6 Avian Influenza Virus in China

The clade 2.3.4.4b H5N8 avian influenza viruses (AIVs) have caused the loss of more than 33 million domestic poultry worldwide since January 2020. Novel H5N6 reassortants with hemagglutinin (HA) from clade 2.3.4.4b H5N8 AIVs are responsible for multiple human infections in China. Therefore, we conducted an epidemiological survey on waterfowl farms in Sichuan and Guangxi provinces and performed a comprehensive spatiotemporal analysis of H5N6 AIVs in China. At the nucleotide level, the H5N6 AIVs isolated in the present study exhibited high homology with the H5N6 AIVs that caused human infections. Demographic history indicates that clade 2.3.4.4b seemingly replaced clade 2.3.4.4h to become China's predominant H5N6 AIV clade. Based on genomic diversity, we classified clade 2.3.4.4b H5N6 AIV into ten genotypes (2.3.4.4bG1-G10), of which the 2.3.4.4bG5 and G10 AIVs can cause human infections. Phylogeographic results suggest that Hong Kong and Jiangxi acted as important epicentres for clades 2.3.4.4b and 2.3.4.4h, respectively. Taken together, our study provides critical insight into the evolution and spread of H5N6 AIVs in China, which indicates that the novel 2.3.4.4b reassortants pose challenges for public health and poultry.