Amino acid substitutions involved in the adaptation of a novel highly pathogenic H5N2 avian influenza virus in mice.
Amino acid substitutions involved in the adaptation of a novel highly pathogenic H5N2 avian influenza virus in mice.
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氨基酸取代参与新型高致病性 H5N2 禽流感病毒在小鼠体内的适应
DOI：
10.1186/s12985-016-0612-5
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发表时间：
2016-09-23
期刊：
影响因子：
4.8
通讯作者：
Wu N
中科院分区：
文献类型：
--
作者：
Wu H;Peng X;Peng X;Wu N
背景H5N2型禽流感病毒(AIV)可感染与受感染禽类有频繁接触的个体。2013年，我们从中国东部的一只鸭中分离到一株新的高致病性H5N2型禽流感病毒重配株[A/鸭子/浙江/6DK19/2013(H5N2)(6DK19)]。这项研究是为了了解导致6DK19在哺乳动物中复制增强和毒力增加的适应性过程。6DK19通过连续的肺对肺传代(共10代)适应于小鼠。测定了野毒株(WT-6DK19)和小鼠适应株(MA-6DK19)对小鼠的毒力。发现MA-DK19 PB2(E627K)、PB1(I181T)、HA(A150S)、NS1(C端7个氨基酸延伸)和NS2(E69G)蛋白的氨基酸序列发生了变化。存活和组织学分析表明，MA-6DK19对小鼠的毒力强于WT-6DK19。结论这些变异与H5N2型禽流感病毒在哺乳动物体内的复制效率和毒力增强有关。需要继续监测携带这些突变的家禽中的H5N2病毒。
BackgroundH5N2 avian influenza viruses (AIVs) can infect individuals that are in frequent contact with infected birds. In 2013, we isolated a novel reassortant highly pathogenic H5N2 AIV strain [A/duck/Zhejiang/6DK19/2013(H5N2) (6DK19)] from a duck in Eastern China. This study was undertaken to understand the adaptive processes that led enhanced replication and increased virulence of 6DK19 in mammals. 6DK19 was adapted to mice using serial lung-to-lung passages (10 passages total). The virulence of the wild-type virus (WT-6DK19) and mouse-adapted virus (MA-6DK19) was determined in mice. The whole-genome sequences of MA-6DK19 and WT-6DK19 were compared to determine amino acid differences.FindingsAmino acid changes were identified in the MA-DK19 PB2 (E627K), PB1 (I181T), HA (A150S), NS1 (seven amino acid extension “WRNKVAD” at the C-terminal), and NS2 (E69G) proteins. Survival and histology analyses demonstrated that MA-6DK19 was more virulent in mice than WT-6DK19.ConclusionOur results suggest that these substitutions are involved in the enhanced replication efficiency and virulence of H5N2 AIVs in mammals. Continuing surveillance for H5N2 viruses in poultry that are carrying these mutations is required.
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影响因子：
6.7
作者：
Yang H;Chen LM;Carney PJ;Donis RO;Stevens J
通讯作者：
Stevens J
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影响因子：
4.6
作者：
Wu H;Peng X;Peng X;Cheng L;Lu X;Jin C;Xie T;Yao H;Wu N
通讯作者：
Wu N
影响因子：
3.7
作者：
Crusat, Martin;Liu, Junfeng;Palma, Angelina S.;Childs, Robert A.;Liu, Yan;Wharton, Stephen A.;Lin, Yi Pu;Coombs, Peter J.;Martin, Stephen R.;Matrosovich, Mikhail;Chen, Zi;Stevens, David J.;Vo Minh Hien;Tran Tan Thanh;Le Nguyen Truc Nhu;Lam Anh Nguyet;Do Quang Ha;van Doorn, H. Rogier;Tran Tinh Hien;Conradt, Harald S.;Kiso, Makoto;Gamblin, Steve J.;Chai, Wengang;Skehel, John J.;Hay, Alan J.;Farrar, Jeremy;de Jong, Menno D.;Feizi, Ten
通讯作者：
Feizi, Ten
影响因子：
5.4
作者：
Gu, Min;Huang, Junqing;Liu, Xiufan
通讯作者：
Liu, Xiufan
影响因子：
5.4
作者：
Ping, Jihui;Dankar, Samar K.;Brown, Earl G.
通讯作者：
Brown, Earl G.