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中国杭州 2009-2011 年连续季节甲型 H1N1 pdm09 流感病毒血凝素(HA)基因的分子进化:几个具有免疫逃逸变异但没有正选择位点的变异株。

Molecular evolution of HA gene of the influenza A H1N1 pdm09 strain during the consecutive seasons 2009-2011 in Hangzhou, China: several immune-escape variants without positively selected sites.

机构信息

Microbiology Laboratory, Hangzhou Center for Disease Control and Prevention, Zhejiang 310021, China.

出版信息

J Clin Virol. 2012 Dec;55(4):363-6. doi: 10.1016/j.jcv.2012.08.006. Epub 2012 Aug 22.

DOI:10.1016/j.jcv.2012.08.006
PMID:22921413
Abstract

BACKGROUND

Even under immune pressure, the highly active influenza A H1N1 pdm09 variants emerged again in December 2010. Did the variability lead to poor vaccine effectiveness?

OBJECTIVES

To study the genetic distance and antigenic drift of the influenza A H1N1 pdm09 strains based on the sequence analysis of HA virus gene segments during consecutive seasons 2009-2011 in Hangzhou, China.

STUDY DESIGN

39 Clinical samples from influenza-like-illness patients with culture-confirmed influenza A H1N1 pdm09 infections were collected over seasons in routine influenza surveillance. The HA gene was amplified and sequenced. A perspective analysis of genetic distance, antigenic drift and positively selected sites were conducted.

RESULTS

Analyses of human influenza A H1N1 pdm09 strains isolated in Hangzhou revealed that during the seasons 2009-2011, the antigenic drift had occurred, away from the northern hemisphere 2010/2011 influenza vaccine strain A/California/07/2009. The 2010/2011 viruses cluster in two main branches with a significant genetic distance, characterized by either S202T and S468N, or K180T/I, V216A, P288S, I312V and I389F. Interestingly, the epitopes corresponding to the immune-escape characteristic have altered much, but none of the amino acid substitutions in 2010/2011 variants were positively selected.

CONCLUSIONS

The results of genetic surveillance in this study might account for frequent outbreaks of the influenza A H1N1 pdm09 strains since December 2010 and the disappearance after three months circulation. It facilitates early detection of antigenic sites for the virus to escape immunological restraint in 2010/2011 season. Continuous monitoring of antigenic changes is recommended.

摘要

背景

即使在免疫压力下,高度活跃的甲型 H1N1 pdm09 变体也于 2010 年 12 月再次出现。这种变异性是否导致疫苗效果不佳?

目的

基于中国杭州连续三个季节(2009-2011 年)甲型 H1N1 pdm09 株血凝素(HA)病毒基因片段的序列分析,研究流感 A H1N1 pdm09 株的遗传距离和抗原漂移。

研究设计

在常规流感监测中,收集了 39 例经培养证实的流感 A H1N1 pdm09 感染患者的临床样本。扩增和测序 HA 基因。进行遗传距离、抗原漂移和正选择位点的前瞻性分析。

结果

对杭州分离的人感染甲型 H1N1 pdm09 株的分析表明,在 2009-2011 个季节中,发生了抗原漂移,远离北半球 2010/2011 流感疫苗株 A/加利福尼亚/07/2009。2010/2011 年的病毒聚类为两个主要分支,具有显著的遗传距离,特征是 S202T 和 S468N 或 K180T/I、V216A、P288S、I312V 和 I389F。有趣的是,与免疫逃逸特征相对应的表位变化很大,但 2010/2011 年变异株中没有氨基酸取代被正向选择。

结论

本研究的遗传监测结果可能解释了自 2010 年 12 月以来甲型 H1N1 pdm09 株的频繁暴发以及三个月后消失的原因。这有助于早期发现病毒逃避 2010/2011 年免疫抑制的抗原位点。建议持续监测抗原变化。

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