Genetic characterization of EV71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype D and recent emergence of a distinct lineage of subgenotype C2 in Hong Kong.
Genetic characterization of EV71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype D and recent emergence of a distinct lineage of subgenotype C2 in Hong Kong.
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DOI：
10.1186/1743-422x-10-222
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发表时间：
2013-07-04
期刊：
影响因子：
4.8
通讯作者：
Yuen KY
中科院分区：
文献类型：
--
作者：
Yip CC;Lau SK;Lo JY;Chan KH;Woo PC;Yuen KY
肠病毒71型（EV71）是儿童手足口病（手足口病）的常见病原体。近年来，香港有EV71型病毒流行的报告，但在本港流行的EV71型病毒株的遗传信息有限。本研究的目的是调查7年来香港这些EV71分离株的遗传进化。采用部分VP2-VP3、2C和3D区对2004-2010年从香港分离的22株EV71进行系统发育分析。选取8株EV71进行全基因组测序和重组分析。根据部分VP2-VP3、2C和3D基因区系统发育分析，22株EV71分离株中有20株属于C4亚基因型，2株属于C2亚基因型。对7个C4亚型EV71分离株的全基因组序列进行系统发育、相似图和bootscan分析，支持在香港持续流行的C4亚型“双重组”菌株属于一种新提出的基因型d。进一步分析显示，C4b和C4a亚型（分别为提议的基因型D1a和D1b）有两个聚类，其中“基因型D1b”菌株近年在香港占主导地位。2008年在香港出现了一个独特的EV71亚型C2谱系。EV71的进化速率为3.1 × 10-3个核苷酸/位点/年，与EV68等其他肠道病毒相似，但相对低于埃可病毒30和脊髓灰质炎病毒。利用VP1基因的分子钟分析将所有EV71基因型的最近共同祖先追溯到1900年代，而早在1998年就检测到EV71基因型的“双重组”株。该研究为提出新的EV71“D基因型”和确定C2亚基因型的离散谱系提供了分子基础。“基因型D”型EV71毒株已在香港流行超过7年，其中以“基因型D1b”为主。
Enterovirus 71 (EV71) is a common etiological agent of hand, foot and mouth disease (HFMD) in children. EV71 epidemics have been reported in Hong Kong in recent years, and yet the genetic information of EV71 strains circulating in our locality is limited. The objective of this study was to investigate the genetic evolution of these EV71 isolates in Hong Kong over a 7-year period. Twenty-two EV71 isolates from Hong Kong during 2004–2010 were included for phylogenetic analysis using partial VP2-VP3, 2C and 3D regions. Eight EV71 strains were selected for complete genome sequencing and recombination analysis. Among the 22 EV71 isolates, 20 belonged to subgenotype C4 and 2 belonged to subgenotype C2 based on the phylogenetic analysis of partial VP2-VP3, 2C and 3D gene regions. Phylogenetic, similarity plot and bootscan analyses using complete genome sequences of seven EV71 isolates of subgenotype C4 supported that the “double-recombinant” strains of subgenotype C4 persistently circulating in Hong Kong should belong to a newly proposed genotype D. Further analysis revealed two clusters, subgenotypes C4b and C4a (proposed genotypes D1a and D1b respectively), with “genotype D1b” strains being predominant in recent years in Hong Kong. A distinct lineage of EV71 subgenotype C2 has emerged in Hong Kong in 2008. The evolutionary rate of EV71 was 3.1 × 10-3 nucleotide substitutions per site per year similar to that of other enterovirus, such as EV68, but was relatively lower than those of echovirus 30 and poliovirus. Molecular clock analysis using VP1 gene dated the time to the most recent common ancestor of all EV71 genotypes to 1900s, while the EV71 “double-recombinant” strains of “genotype D” were detected as early as 1998. This study provides the molecular basis for proposing a new “genotype D” of EV71 and assigning a discrete lineage of subgenotype C2. EV71 strains of “genotype D” have been circulating in Hong Kong for over 7 years, with “genotype D1b” being predominant.