Junhan Li, Fang Huang, Yong Zhang, Tianjiao Ji, Shuangli Zhu, Dongyan Wang, Zhenzhi Han, Jinbo Xiao, Fenfen Si, Wenbo Xu and Dongmei Yan. Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing, China[J]. Virologica Sinica, 2022, 37(2): 168-176. doi: 10.1016/j.virs.2022.01.024
Citation: Junhan Li, Fang Huang, Yong Zhang, Tianjiao Ji, Shuangli Zhu, Dongyan Wang, Zhenzhi Han, Jinbo Xiao, Fenfen Si, Wenbo Xu, Dongmei Yan. Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing, China .VIROLOGICA SINICA, 2022, 37(2) : 168-176.  http://dx.doi.org/10.1016/j.virs.2022.01.024

引起1988、1994和2007年北京三起急性出血性结膜炎暴发的柯萨奇A组24型变异株的分子分析

  • 柯萨奇病毒A组24型变异株(CVA24v)是引起急性出血性结膜炎(AHC)持续暴发和大流行的主要病原体。中国首次证实由CVA24v引起的AHC发生在1988年的北京,1994年和2007年在北京再次暴发了两起AHC,这三起暴发与20世纪70年代以后AHC在世界范围内流行的三个阶段动态分布相一致。为阐明不同时期CVA24v的遗传特征,从3次暴发中共分离到23株CVA24v,并对其全基因组进行测序及分析。与原型株相比,除2007年分离的0744株外,其余分离株均在5'UTR有4个核苷酸缺失。2007年分离株中的第98个位点均有一个核苷酸的插入。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。基于3C和VP1建立的系统发育树均表明,1988年和1994年分离株属于基因型III (GIII), 2007年分离株属于基因型IV (GIV)。基于全基因组序列的贝叶斯分析表明,1988年、1994年和2007年分离株的最近共同祖先分别估算为1987年10月、1993年2月和2004年12月左右。CVA24v的进化速率估计为7.45×10-3 substitute /site/year。我们的研究表明,CVA24v在中国大陆的早期流行为GIII基因型。不同基因型CVA24v的点突变和氨基酸变化可能导致AHC暴发强度的差异。CVA24v一直以相对较快的速度不断进化。

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

  • Corresponding author: Dongmei Yan, dongmeiyan1976@163.com
  • Received Date: 28 January 2021
    Accepted Date: 14 January 2022
  • 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 7.45×10-3 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.

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

      Corresponding author: Dongmei Yan, dongmeiyan1976@163.com
    • a 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

    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 7.45×10-3 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.

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