中国深圳 1998-2013 年肠道病毒 A71 亚型 C4 的遗传进化。

Genetic evolution of Human Enterovirus A71 subgenotype C4 in Shenzhen, China, 1998-2013.

机构信息

Shenzhen Center for Disease Control and Prevention, Shenzhen, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, China.

JC School of Public Health and Primary Care, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

出版信息

J Infect. 2016 Jun;72(6):731-737. doi: 10.1016/j.jinf.2016.03.014. Epub 2016 Mar 31.

DOI:10.1016/j.jinf.2016.03.014

PMID:27038503

Abstract

BACKGROUND

Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (HFMD) among children. This study identified the mutations of EV-A71 VP1 amino acid residues over a number of years and explored the possible association of identified mutations and HFMD epidemic outbreaks in Shenzhen, China.

METHODS

A total of 3760 stool specimens were collected from HFMD patients by Shenzhen Centers for Disease Control and Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced in this study, and amino acids mutation frequency was calculated. There were 2040 China nationwide sequences downloaded from Genebank as replication data.

RESULTS

In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid positions on VP1 protein were found to have high mutation prevalence. These are Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008, at the time of the large scale epidemic outbreak in Shenzhen. Analysis of the nationwide data replicated the same trend of mutation prevalence of the three sites.

CONCLUSION

The switching from Q to H on site 22 of the EV-A71 VP1 strain might be associated with the HFMD outbreak in Shenzhen in 2008. The identified amino acid sites 22, 283 and 289 provided information for developing anti-viral drugs against EV-A71 in the future.

摘要

背景

肠道病毒 A71 型（EV-A71）是人肠道病毒的一种，是引起儿童手足口病（HFMD）的最严重病原体之一。本研究对 EV-A71 VP1 氨基酸残基的多年突变进行了鉴定，并探讨了在中国深圳发现的突变与 HFMD 流行爆发之间的可能关联。

方法

1998 年至 2013 年间，深圳市疾病预防控制中心（CDC）从 HFMD 患者中采集了 3760 份粪便标本。本研究共对 289 株 VP1 株进行了测序，并计算了氨基酸突变频率。从 Genebank 下载了 2040 株中国全国范围内的序列作为复制数据。

结果

在我们的样本中，有 1036 名（27.6%）患者为 EV-A71 感染。VP1 蛋白上有 3 个氨基酸位置的突变发生率较高。分别是 Q22H、S283T 和 A289H。位点 22 在 2008 年出现了快速突变固定，当时深圳发生了大规模的流行爆发。对全国范围内的数据进行分析，复制了这三个位点的突变发生率相同的趋势。