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2009年大流行期间从肯尼亚分离出的甲型H1N1pdm09人流感病毒的全基因组特征分析

Whole genome characterization of human influenza A(H1N1)pdm09 viruses isolated from Kenya during the 2009 pandemic.

作者信息

Gachara George, Symekher Samuel, Otieno Michael, Magana Japheth, Opot Benjamin, Bulimo Wallace

机构信息

Department of Medical Laboratory Sciences, Kenyatta University, Kenya.

Centre for Virus Research, KEMRI, Kenya.

出版信息

Infect Genet Evol. 2016 Jun;40:98-103. doi: 10.1016/j.meegid.2016.02.029. Epub 2016 Feb 26.

Abstract

An influenza pandemic caused by a novel influenza virus A(H1N1)pdm09 spread worldwide in 2009 and is estimated to have caused between 151,700 and 575,400 deaths globally. While whole genome data on new virus enables a deeper insight in the pathogenesis, epidemiology, and drug sensitivities of the circulating viruses, there are relatively limited complete genetic sequences available for this virus from African countries. We describe herein the full genome analysis of influenza A(H1N1)pdm09 viruses isolated in Kenya between June 2009 and August 2010. A total of 40 influenza A(H1N1)pdm09 viruses isolated during the pandemic were selected. The segments from each isolate were amplified and directly sequenced. The resulting sequences of individual gene segments were concatenated and used for subsequent analysis. These were used to infer phylogenetic relationships and also to reconstruct the time of most recent ancestor, time of introduction into the country, rates of substitution and to estimate a time-resolved phylogeny. The Kenyan complete genome sequences clustered with globally distributed clade 2 and clade 7 sequences but local clade 2 viruses did not circulate beyond the introductory foci while clade 7 viruses disseminated country wide. The time of the most recent common ancestor was estimated between April and June 2009, and distinct clusters circulated during the pandemic. The complete genome had an estimated rate of nucleotide substitution of 4.9×10(-3) substitutions/site/year and greater diversity in surface expressed proteins was observed. We show that two clades of influenza A(H1N1)pdm09 virus were introduced into Kenya from the UK and the pandemic was sustained as a result of importations. Several closely related but distinct clusters co-circulated locally during the peak pandemic phase but only one cluster dominated in the late phase of the pandemic suggesting that it possessed greater adaptability.

摘要

一种新型甲型H1N1流感病毒(A(H1N1)pdm09)引发的流感大流行于2009年在全球蔓延,据估计全球死亡人数在151,700至575,400人之间。虽然新病毒的全基因组数据能让我们更深入地了解流行病毒的发病机制、流行病学和药物敏感性,但来自非洲国家的该病毒完整基因序列相对有限。我们在此描述2009年6月至2010年8月期间在肯尼亚分离出的甲型H1N1流感病毒(A(H1N1)pdm09)的全基因组分析。共选取了大流行期间分离出的40株甲型H1N1流感病毒(A(H1N1)pdm09)。对每个分离株的基因片段进行扩增并直接测序。将各个基因片段的所得序列拼接起来用于后续分析。这些序列用于推断系统发育关系,还用于重建最近共同祖先的时间、引入该国的时间、替换率以及估计时间分辨系统发育。肯尼亚的完整基因组序列与全球分布的2类和7类序列聚类,但本地的2类病毒未在引入地点之外传播,而7类病毒在全国范围内传播。最近共同祖先的时间估计在2009年4月至6月之间,大流行期间有不同的聚类在传播。完整基因组的核苷酸替换率估计为4.9×10(-3)替换/位点/年,且观察到表面表达蛋白的多样性更大。我们表明,甲型H1N1流感病毒(A(H1N1)pdm09)的两个分支从英国引入肯尼亚,并且由于病毒输入大流行得以持续。在大流行高峰期,几个密切相关但不同的聚类在当地共同传播,但在大流行后期只有一个聚类占主导,这表明它具有更强的适应性。

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