Abstract
Avian influenza A viruses (AIVs) H5N1, first identified in 1996, are highly pathogenic in domestic poultry and continue to occasionally infect humans. In this study, we sought to identify genetic changes that occurred during their multiple invasions to humans. We evaluated all available H5Nx AIV genomes. Significant signals of positive selection were detected in 29 host-shift branches. 126 parallel evolution sites were detected on these branches, including 17 well-known sites (such as T271A, A274T, T339M, Q591K, E627K, and D701N in PB2; A134V, D154N, S223N, and R497K in HA) that play roles in allowing AIVs to cross species barriers. Our study suggests that during human infections, H5Nx viruses have experienced adaptive evolution (positive selection and convergent evolution) that allowed them to adapt to their new host environments. Analyses of adaptive evolution should be useful in identifying candidate sites that play roles in human infections, which can be tested by functional experiments.
Highlights
Avian influenza viruses (AIVs) pose a continuous threat to public health due to their pandemic potential (Widdowson et al, 2017)
H5Nx viruses do not have the ability to be transmitted efficiently in a sustained manner from personto-person, these highly pathogenic avian virus (HPAIV), which are panzootic in poultry, continue to spread, and their interspecific transmission poses a major challenge to human health
Sporadic human infections continue to occur in countries where H5Nx have become endemic in birds, providing a persistent threat to global health due to the possibility of virus adaptation to humans
Summary
Avian influenza viruses (AIVs) pose a continuous threat to public health due to their pandemic potential (Widdowson et al, 2017). H5 is the predominate AIV subtype that infect human populations, and pose great threat to public health (Peiris et al, 2007). Adaptive Evolution of H5Nx AIVs are observed on multiple evolutionary lineages, convergent or parallel amino acid changes in key genes occur (Zhang, 2006; Shen et al, 2012). Our previous study showed that during the multiple invasions of humans by H7N9 AIVs, convergent evolution occurred to allow these human-isolated viruses to adapt their new hosts (Xiang et al, 2018). H5Nx viruses do not have the ability to be transmitted efficiently in a sustained manner from personto-person, these HPAIVs, which are panzootic in poultry, continue to spread, and their interspecific transmission poses a major challenge to human health. We conducted a comprehensive evolutionary analysis of H5Nx viruses by collecting all available sequence data to examine molecular mechanisms used by H5Nx viruses to frequently infect humans
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