2008年广东省肠道病毒71型分离株全基因组核苷酸序列分析

The complete sequence analysis of Enterovirus 71 strain from the fatal case of the hand, foot and mouth disease during an epidemic of Guangdong province in 2008

目的了解2008年广东省流行的肠道病毒（EV）71型基因特征。方法选择2008年广东省分离的1株EV71毒株（GDFS-3），进行全基因组序列测定和基因进化特性的分析。结果GDFS-3株与其他EV71型毒株相比，在编码区没有核苷酸的缺失和插入，其5’UTR和3’UTR的长度和序列有一定的差异。核苷酸同源性比较结果表明，GDFS-3株与中国台湾流行株（TW984）的同源性最高（为96．0％），与新加坡流行株SIN5865及标准株MS、BrCr的同源性则在81．0％左右。氨基酸同源性比较结果表明，GDFS-3株与TW984同源性最高（99．0％）。根据VP1基因序列构建亲缘性关系树，GDFS-3株与C4亚型（subgenogroup）聚为一簇，与C4亚型代表株的核苷酸序列同源性为91．0％-95．0％。结论遗传进化分析表明，GDFS-3株和中国台湾2004年流行的EV71毒株的亲缘关系最为密切，属于C4亚型，而与标准株BrCr和MS的亲缘关系较远。5＇UTR的突变对于EV71毒力增强可能有重要作用。上述结果有助于EV71型的基础研究和中国对于EV71所致疾病的预防。

Objective To Understand the genetic characteristics of Enterovirus 71 （ EV71 ） circulating strains of Guangdong province in 2008. Methods We isolated an EV71 strain from the fatal case of the hand, foot and mouth disease during an epidemic of Guangdong in 2008. Its complete genome was sequenced and analyzed comparatively. Results The results showed that the full length of EV71 GDFS-3 genome （ not including poly A tail） is 7405 bp. No insertion or deletion is detected in the coding region. There are several insertions and deletions in 5 ＇and 3 ＇UTR. Phylogenetic analysis of GDFS-3 and reference strains showed GDFS-3 strain shares the highest nucleotide homology with TW984 strain（96.0% ） but low homology with SIN5865, MS and BrCr（ about 81.0% ）. GDFS-3 strain also shares the highest amino acid homology with TW984 strain（99.0% ）. It clustered with reference strains of CA subgenotype in the phylogenetic tree. The nucleotide identity with CA reference strains is 91.0% -95.0%. Conclusion The phylogenetic analysis based on the entire genome demonstrates that GDFS-3 strain has the nearest genetic relationship with TW984 strains （isolated in 2004）. GDFS-3 may belong to the same subgenogroup （CA）with Taiwan predominant strains. Otherwise, Some mutations in 5＇UTR of EV71 may play the very important role in heightened virulence.