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中国北京 1988 年、1994 年和 2007 年三次急性出血性结膜炎暴发中分离的柯萨奇病毒 A24 变异株的分子分析。

Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing, China.

机构信息

National Polio Laboratory, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosecurity, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China; Nanguan District Center for Disease Control and Prevention, Changchun, 130042, China.

Beijing Center for Disease Control and Prevention, Beijing, 100000, China.

出版信息

Virol Sin. 2022 Apr;37(2):168-176. doi: 10.1016/j.virs.2022.01.024. Epub 2022 Jan 22.

DOI:10.1016/j.virs.2022.01.024
PMID:35277374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9170931/
Abstract

Coxsackievirus A24 variant (CVA24v) is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC). In China, the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988, followed by another two significant outbreaks respectively in 1994 and 2007, which coincides with the three-stage dynamic distribution of AHC in the world after 1970s. To illustrate the genetic characteristics of CVA24v in different periods, a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed. Compared with the prototype strain, the 23 strains shared four nucleotide deletions in the 5' UTR except the 0744 strain isolated in 2007. And at the 98th site, one nucleotide insertion was found in all the strains collected from 2007. From 1994 to 2007, amino acid polarity in the VP1 region at the 25th and the 32nd site were changed. Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III (GIII), and 2007 strains to Genotype IV (GIV). According to the Bayesian analysis based on complete genome sequence, the most recent common ancestors for the isolates in 1988, 1994 and 2007 were respectively estimated around October 1987, February 1993 and December 2004. The evolutionary rate of the CVA24v was estimated to be 7.45 ​× ​10 substitutions/site/year. Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII. Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak. CVA24v has been evolving constantly with a relatively rapid rate.

摘要

柯萨奇病毒 A24 变体(CVA24v)是引起急性出血性结膜炎(AHC)持续爆发和流行的主要病原体。在中国,首例确诊的 CVA24v 相关 AHC 爆发于 1988 年的北京,随后分别于 1994 年和 2007 年又爆发了两次重大疫情,这与 20 世纪 70 年代后全球 AHC 的三阶动态分布一致。为了说明不同时期 CVA24v 的遗传特征,从这三次疫情中总共分离出 23 株病毒,并对这些分离株的全基因组进行了测序和分析。与原型株相比,除 2007 年分离的 0744 株外,23 株病毒在 5'UTR 中有四个核苷酸缺失。在所有 2007 年采集的病毒株中,在第 98 位发现了一个核苷酸插入。从 1994 年到 2007 年,VP1 区第 25 位和第 32 位的氨基酸极性发生了变化。3C 和 VP1 系统发育树均表明,1988 年和 1994 年分离的病毒株属于基因型 III(GIII),而 2007 年的病毒株属于基因型 IV(GIV)。根据基于全基因组序列的贝叶斯分析,1988 年、1994 年和 2007 年分离株的最近共同祖先分别估计在 1987 年 10 月左右、1993 年 2 月和 2004 年 12 月。CVA24v 的进化率估计为 7.45×10 取代/位点/年。本研究表明,中国大陆早期 CVA24v 流行株为 GIII。不同基因型 CVA24v 的点突变和氨基酸变化可能导致 AHC 爆发的强度差异。CVA24v 一直在不断进化,进化速度相对较快。

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