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PB2 and HA mutations increase the virulence of highly pathogenic H5N5 clade 2.3.4.4 avian influenza virus in mice

文献类型： 外文期刊

作者： Yu, Zhijun 1 ; Cheng, Kaihui 4 ; Sun, Weiyang 2 ; Zhang, Xinghai 2 ; Xia, Xianzhu 2 ; Gao, Yuwei 2 ;

作者机构： 1.Shandong Acad Agr Sci, Inst Poultry Sci, 1 Jiaoxiao Rd, Jinan 250023, Shandong, Peoples R China

2.Acad Mil Med Sci, Mil Vet Res Inst, Key Lab Jilin Prov Zoonosis Prevent & Control, Changchun 130122, Jilin, Peoples R China

3.Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China

4.Shandong Acad Agr Sci, Dairy Cattle Res Ctr, Jinan 250132, Shandong, Peoples R China

5.Acad Mil Med Sci, Mil Vet Inst, 666 Liuyingxi St, Changchun 130122, Jilin, Peoples R China

6.Acad Mil Med Sci, Mil Vet Inst, 666 Liuyingxi St, Changchun 1

期刊名称：ARCHIVES OF VIROLOGY （ 影响因子：2.574； 五年影响因子：2.466 ）

ISSN： 0304-8608

年卷期： 2018 年 163 卷 2 期

页码：

收录情况： SCI

摘要： H5 clade 2.3.4.4 influenza A viruses pose a potential threat to public health and are a cause of public concern. Here, we generated mouse-adapted viruses of a waterfowl-origin H5N5 virus (H5 clade 2.3.4.4) to identify adaptive changes that confer increased virulence in mammals. After two passages, we obtained a mouse-adapted H5N5 virus that contained single amino acid substitutions in the PB2 (E627K) and hemagglutinin (HA) (F430L) proteins. We then analyzed the impact of these individual amino acid substitutions on viral pathogenicity to mammals. The 50% mouse lethal dose (MLD50) of the H5N5 virus containing the PB2-E627K substitution or the HA-F430L substitution was reduced 1000-fold or 3.16-fold, respectively. Furthermore, we found that PB2-E627K enhanced viral replication kinetics in vitro and in vivo. These results suggest that the PB2-E627K and HA-F430L substitutions are important for adaptation of H5N5 AIVs to mammals. These findings emphasize the importance of continued surveillance of poultry for H5N5 AIVs with these amino acid substitutions.

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