Guo Fucheng, Li Yiliang, Yu Shu, Liu Lu, Luo Tingting, Pu Zhiqing, Xiang Dan, Shen Xuejuan, Irwin David M, Liao Ming, Shen Yongyi
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Joint Influenza Research Centre (SUMC/HKU), Shantou University Medical College, Shantou, China.
Front Microbiol. 2019 Jun 12;10:1328. doi: 10.3389/fmicb.2019.01328. eCollection 2019.
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.
1996年首次发现的甲型禽流感病毒（AIV）H5N1在家禽中具有高致病性，并持续偶尔感染人类。在本研究中，我们试图确定其多次感染人类过程中发生的基因变化。我们评估了所有可用的H5Nx AIV基因组。在29个宿主转移分支中检测到显著的正选择信号。在这些分支上检测到126个平行进化位点，包括17个知名位点（如PB2中的T271A、A274T、T339M、Q591K、E627K和D701N；HA中的A134V、D154N、S223N和R497K），这些位点在AIV跨越物种屏障中发挥作用。我们的研究表明，在人类感染期间，H5Nx病毒经历了适应性进化（正选择和趋同进化），使其能够适应新的宿主环境。适应性进化分析有助于识别在人类感染中起作用的候选位点，这些位点可通过功能实验进行验证。
