[2013-2014年湖北省甲型流感H1N1pdm09病毒卵适应突变分析]。

Bin Fang, Linlin Liu, Guojun Ye, Xiang Li, Xiao Yu, Yongzhong Jiang
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摘要

甲型流感H1N1pdm09病毒;鸡胚胎;系统发育树;Egg-adaptation;抗原网站;耐药性网站;摘要:为研究湖北省流感监测网分离的甲型H1N1pdm09流感病毒的蛋适应突变,对鸡胚分离的三种甲型H1N1pdm09流感病毒与相应的MDCK细胞源病毒进行了比较分析。分析包括检查系统发育树、进化速率、氨基酸替换、适应卵子的突变和同源性模型。基于系统发育树和进化速率,我们发现蛋适应病毒和MDCK细胞衍生病毒之间存在差异;病毒呈“NA>HA>MP”的趋势。在3种卵适应病毒中发现了Q223R、v527i、m19i和H275Y 4个氨基酸取代。血凝素蛋白中检测到Q223和v527i,神经氨酸酶中检测到M19I和H275Y。Q223R突变改变了Sb和Ca2之间的抗原位点结构。H275Y是一种典型的神经氨酸酶耐药突变。结果提示,从湖北省流感监测网的鸡胚中分离流感病毒时引入了鸡蛋适应突变。这些突变可能影响候选疫苗的选择和疫苗效力;因此,在流感监测网络中应加强对鸡蛋适应突变的监测。
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[Analysis of Egg-adapted Mutations in Influenza A H1N1pdm09 Viruses in Hubei Province of China, 2013-2014].

Influenza A H1N1pdm09 Virus; Chicken embryo; Phylogenetic tree; Egg-adaptation; Antigenic site; Drug-resistance site; Abstract: To investigate egg-adapted mutation in influenza A H1N1pdm09 viruses isolated from the Hubei influenza surveillance network, a comparative analysis was performed of three influenza A H1N1pdm09 viruses isolated in chicken embryo and the corresponding MDCK cell-derived viruses. Analyses included examination of the phylogenetic tree, evolutionary rates, amino acid substitutions, egg-adapted mutation and homology modeling. We found differences between the egg-adapted viruses and MDCK cell-derived viruses based on phylogenetic trees and evolutionary rates; the viruses showed a trend of " NA>HA>MP". Four amino acid substitutions(Q223R,V527 I,M19Iand H275Y)were found in three egg-adapted viruses.Q223 Rand V527Iwere present in the haemagglutinin protein, while M19I and H275Y were detected in neuraminidase.The Q223R mutation changed the structure of antigenic sites between Sb and Ca2. H275Y is a classic neuraminidase resistance mutation. The results suggest that the egg-adapted mutations were introduced when influenza viruses were isolated in chicken embryos from the Hubei influenza surveillance network. These mutations may affect the selection of vaccine candidates and vaccine efficacy; therefore, monitoring of egg-adapted mutations should be strengthened in the influenza surveillance network.

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