Multiple amino acid substitutions involved in the virulence enhancement of an H3N2 avian influenza A virus isolated from wild waterfowl in mice
文献类型： 外文期刊
作者： Yu, Zhijun 1 ; Sun, Weiyang 2 ; Zhang, Xinghai 2 ; Cheng, Kaihui 4 ; Zhao, Chuqi 5 ; Gao, Yuwei 2 ; Xia, Xianzhu 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.Yanbian Univ, Agr Coll, Dept Anim Sci, Yanji 133002, Peoples R China
关键词： Avian influenza A virus; H3N2; Wild birds; Mice; Pathogenicity
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： Frequent emergence of low pathogenic avian influenza H3N2 viruses in the wild birds has caused concern for human health. Here, we generated mouse-adapted strains of a wild waterfowl-origin low pathogenic avian influenza H3N2 virus to identify adaptive mutations that confer enhanced virulence in mammals. The mouse lethal doses (MLD50) of the adapted strains were reduced > 562-fold compared to the parental virus. Mouse-adapted strains displayed enhanced replication in vitro and in vivo, and acquired the ability to replicate in extrapulmonary tissues. These observations suggest that enhanced growth characteristics and modified cell tropism may increase the virulence of H3N2 AIVs in mice. Genomic analysis revealed mutations in the PB2 (E192 K and D701N), PB1 (F269S, 1475 V, and L598P), HA (V242E), NA (G170R), and M1 (M192 V) proteins. Our results suggest that these amino acid substitutions collaboratively enhance the ability of H3N2 avian influenza A virus to replicate and cause severe disease in mammals.
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