Multiple adaptive amino acid substitutions increase the virulence of a wild waterfowl-origin reassortant H5N8 avian influenza virus in mice

被引：8
作者：
Yu, Zhijun [1 ]
Cheng, Kaihui [4 ]
Sun, Weiyang [2 ]
Zhang, Xinghai [2 ]
Xia, Xianzhu [2 ,3 ,5 ]
Gao, Yuwei [2 ,3 ,5 ]
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] PLA, Acad Mil Med Sci, Mil Vet Inst, 666 Liuyingxi St, Changchun 130122, Jilin, Peoples R China
来源：
VIRUS RESEARCH | 2018年 / 244卷
关键词：
Wild waterfowl; Avian influenza virus; H5N8; Virulence; Mice; ENHANCE POLYMERASE-ACTIVITY; A VIRUS; A(H5N8) VIRUS; QINGHAI LAKE; PB2; GENE; ADAPTATION; TRANSMISSION; PATHOGENESIS; INFECTION; FERRETS;
D O I：
10.1016/j.virusres.2017.11.002
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
A novel H5N8 highly pathogenic avian influenza virus (HPAIV) caused poultry outbreaks in the Republic of Korea in 2014. The novel H5N8 HPAIV has spread to Asia, Europe, and North America and caused great public concern from then on. Here, we generated mouse-adapted variants of a wild waterfowl-origin H5N8 HPAIV to identify adaptive mutants that confer enhanced pathogenicity in mammals. The mouse lethal doses (MLD50) of the mouse-adapted variants were reduced 31623-fold compared to the wild-type (WT) virus. Mouse-adapted variants displayed enhanced replication in vitro and in vivo, and expanded tissue tropism in mice. Sequence analysis revealed four amino acid substitutions in the PB2 (E627K), PA (F35S), HA (R227H), and NA (I462V) proteins. These data suggest that multiple amino acid substitutions collaboratively increase the virulence of a wild bird-origin reassortant H5N8 HPAIV and cause severe disease in mice.
引用
收藏
页码：13 / 20
页数：8
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