Shanghai Veterinary Research Institutegrid.464410.3, Chinese Academy of Agricultural Sciences, Shanghai, China.
Animal Influenza and Emerging Avian Viral Diseases Innovation Team, Shanghai, China.
J Virol. 2021 Sep 9;95(19):e0101921. doi: 10.1128/JVI.01019-21.
Based on our previous studies, we show that the M gene is critical for the replication and pathogenicity of the chimeric H17 bat influenza virus (Bat09:mH1mN1) by replacing the bat M gene with those from human and swine influenza A viruses. However, the key amino acids of the M1 and/or M2 proteins that are responsible for virus replication and pathogenicity remain unknown. In this study, replacement of the PR8 M gene with the Eurasian avian-like M gene from the A/California/04/2009 pandemic H1N1 virus significantly decreased viral replication in both mammalian and avian cells in the background of the chimeric H17 bat influenza virus. Further studies revealed that M1 was more crucial for viral growth and pathogenicity than M2 and that the amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins identified in this study might be important for influenza virus surveillance and could be used to produce live attenuated vaccines in the future. The M1 and M2 proteins influence the morphology, replication, virulence, and transmissibility of influenza viruses. Although a few key residues in the M1 and M2 proteins have been identified, whether other residues of the M1 and M2 proteins are involved in viral replication and pathogenicity remains to be discovered. In the background of the chimeric H17 bat influenza virus, the Eurasian avian-like M gene from the A/California/04/2009 virus significantly decreased viral growth in mammalian and avian cells. Further study showed that M1 was implicated more than M2 in viral growth and pathogenicity and and that the key amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins could be used for influenza virus surveillance and live attenuated vaccine applications in the future. These findings provide important contributions to knowledge of the genetic basis of the virulence of influenza viruses.
基于我们之前的研究，通过用来自人源和猪源流感病毒的 M 基因替换嵌合 H17 蝙蝠流感病毒（Bat09:mH1mN1）的蝙蝠 M 基因，我们表明 M 基因对于该嵌合病毒的复制和致病性至关重要。然而，负责病毒复制和致病性的 M1 和/或 M2 蛋白的关键氨基酸仍然未知。在这项研究中，用来自 A/加利福尼亚/04/2009 大流行 H1N1 病毒的欧亚类禽 M 基因替换 PR8 M 基因，显著降低了嵌合 H17 蝙蝠流感病毒背景下哺乳动物和禽类细胞中的病毒复制。进一步的研究表明，M1 比 M2 对于病毒生长和致病性更为关键，并且 M1-41V 和 M2-27A 氨基酸残基负责细胞和小鼠中的这些特征。本研究中鉴定的 M1 和 M2 蛋白的这些关键残基可能对于流感病毒监测很重要，并可用于未来生产活减毒疫苗。M1 和 M2 蛋白影响流感病毒的形态、复制、毒力和传播性。尽管已经确定了 M1 和 M2 蛋白中的几个关键残基，但 M1 和 M2 蛋白的其他残基是否参与病毒复制和致病性仍有待发现。在嵌合 H17 蝙蝠流感病毒的背景下，来自 A/加利福尼亚/04/2009 病毒的欧亚类禽 M 基因显著降低了哺乳动物和禽类细胞中的病毒生长。进一步的研究表明，M1 比 M2 更能影响病毒生长和致病性，并且关键氨基酸残基 M1-41V 和 M2-27A 负责细胞和小鼠中的这些特征。这些 M1 和 M2 蛋白的关键残基可用于未来的流感病毒监测和活减毒疫苗应用。这些发现为了解流感病毒毒力的遗传基础做出了重要贡献。
