山西省2014年Ⅱ型疫苗衍生脊髓灰质炎病毒的基因特性分析  

Genetic Characteristics of Type 2 Vaccine-derived Poliovirus in Shanxi Province(China) in 2014

作　　者：严冬梅[1] 李晓嫘[1] 张勇[1] 杨建芳[2] 祝双利[1] 王东燕[1] 张创业[2] 朱晖[1] 许文波[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,卫生部医学病毒和病毒病重点实验室,世界卫生组织西太平洋区脊髓灰质炎参比实验室,北京102206 [2]山西省疾病预防控制中心,太原030012

出　　处：《病毒学报》2015年第2期157-163,共7页Chinese Journal of Virology

基　　金：国家自然科学基金(项目批准号81101303和81373049);盖茨基金(OPP 1109760;1045794和1048143)

摘　　要：2010年世界卫生组织（World Health Organization,WHO）对Ⅱ型疫苗衍生脊髓灰质炎（脊灰）病毒（Vaccinederived Poliovirus,VDPV）定义进行了修订,为研究新定义的Ⅱ型VDPV的基因特征及进化,本研究对山西省2014年1例急性弛缓性麻痹（Acute flaccid paralysis,AFP）病例中分离到的1株Ⅱ型VDPV进行全基因组序列测定和分析。测序显示毒株的基因全长为7 439个碱基,共编码2207个氨基酸,与Sabin2疫苗株相比不存在碱基的插入和缺失。该毒株在已知的减毒位点5′非编码区nt481上发生了回复突变,而在另一个减毒位点VP1衣壳编码区nt2909位点上未发生核苷酸变异。毒株与Sabin1发生重组,重组位点位于3D非结构编码区的nt6 247～6 281之间。VP1编码区基因进化树分析表明山西Ⅱ型VDPV的进化独立于国内外至今发现的其它Ⅱ型VDPVs,按照脊灰已知的基因进化速率估算该毒株已在人群中循环约176d。本研究再次证明了中国脊灰实验室网络监测的敏感性,能够及时准确地发现VDPV,在中国维持无脊灰状态过程中发挥重要作用。The World Health Organization redefined the type 2vaccine-derived poliovirus（VDPV）in 2010.To study the genetic characteristics and evolution of type 2VDPV under this new definition,we conducted genome sequencing and analyses of type 2VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province（China）in 2014.Nucleotide sequencing revealed that the full-length of type 2VDPV is7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2.One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2strain（A→G reversion at nucleotide nt 481 in the 5-end of the untranslated region）had reverted in the Shanxi type 2VDPV.The other known key determinant of the attenuated phenotype of the Sabin 2strain（U→C reversion at nt2909 in the VP1 coding region that caused a Ile143 Thr substitution in VP1）had not reverted in the Shanxi VDPV.The Shanxi type 2 VDPV was S2/S1 recombinant,the crossover site of which mapped to the 3-end of the 3Dregion（between nt 6247 and nt 6281）.A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2VDPV was independent of other type 2VDPVs detected worldwide.We estimated that the strain circulated for≈11months in the population according to the known evolution rate.The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China.

关 键 词：山西 疫苗衍生脊髓灰质炎病毒 基因特征 

分 类 号：R373.22[医药卫生—病原生物学]