Rapid acquisition adaptive amino acid substitutions involved in the virulence enhancement of an H1N2 avian influenza virus in mice

文献类型： 外文期刊

第一作者： Yu, Zhijun

作者： Yu, Zhijun;Sun, Weiyang;Zhang, Xinghai;Xia, Xianzhu;Gao, Yuwei;Xia, Xianzhu;Gao, Yuwei;Cheng, Kaihui;Zhao, Chuqi

作者机构：

关键词： Avian influenza virus; H1N2; Wild waterfowl; Adaptation; Mice

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.293； 五年影响因子：3.599 ）

ISSN： 0378-1135

年卷期： 2017 年 207 卷

页码：

收录情况： SCI

摘要： Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2 MV to identify adaptive changes that increased virulence in mammals. MLD50 of the variants were reduced > 1000-fold compared to the parental virus. Variants displayed enhanced replication in vitro and in vivo, and replicate in extrapulmonary organs. These data show that enhanced replication capacity and expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to replicate and cause severe disease in mammals.

分类号： S8

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