A PB1 T296R substitution enhance polymerase activity and confer a virulent phenotype to a 2009 pandemic H1N1 influenza virus in mice

文献类型： 外文期刊

第一作者： Yu, Zhijun

作者： Yu, Zhijun;Qin, Chuan;Xia, Xianzhu;Yu, Zhijun;Qin, Chuan;Xia, Xianzhu;Yu, Zhijun;Sun, Weiyang;Zhang, Xinghai;Li, Yuanguo;Wang, Tiecheng;Wang, Hualei;Xin, Yue;Li, Xue;Zhang, Kun;Huang, Jing;Yang, Songtao;Gao, Yuwei;Xia, Xianzhu;Cheng, Kaihui;Zhang, Qianyi;Chen, Hualan;Wilker, Peter R.;Yue, Donghui;Gao, Yuwei;Xia, Xianzhu;Xia, Xianzhu

作者机构：

关键词： Influenza A virus; H1N1; Mouse model; Virulence

期刊名称：VIROLOGY （ 影响因子：3.616； 五年影响因子：3.967 ）

ISSN： 0042-6822

年卷期： 2015 年 486 卷

页码：

收录情况： SCI

摘要： While the 2009 pandemic H1N1 virus has become established in the human population as a seasonal influenza virus, continued adaptation may alter viral virulence. Here, we passaged a 2009 pandemic H1N1 virus (A/Changchun/01/2009) in mice. Serial passage in mice generated viral variants with increased virulence. Adapted variants displayed enhanced replication kinetics in vitro and vivo. Analysis of the variants genomes revealed 6 amino acid changes in the PB1 (T296R), PA (194V), HA (H3 numbering; N159D, D225G, and R226Q), and NP (D375N). Using reverse genetics, we found that a PB1-T296R substitution found in all adapted viral variants enhanced viral replication kinetics in vitro and vivo, increased viral polymerase activity in human cells, and was sufficient for enhanced virulence of the 2009 pandemic H1N1 virus in mice. Therefore, we defined a novel influenza pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals. (C) 2015 Elsevier Inc. All rights reserved.

分类号： R37

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