四川省2009年Ⅱ型疫苗高变异脊髓灰质炎病毒潜在流行的病毒学分析  

Virological analysis: transmission potential of high mutant type 2 polioviruses in Sichuan,2009

作　　者：严冬梅[1] 陈娜[2] 张勇[1] 祝双利[1] 王东艳[1] 童文彬[2] 朱晖[1] 李晓嫘[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,卫生部医学病毒学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]四川省疾病预防控制中心,成都610041

出　　处：《中国疫苗和免疫》2015年第1期7-11,45,共6页Chinese Journal of Vaccines and Immunization

基　　金：国家自然科学基金青年科学基金项目Ⅱ和Ⅲ型免疫缺陷疫苗衍生脊髓灰质炎病毒在免疫缺陷患者体内复制过程中的动态改变课题(项目批准号81101303);国家自然科学基金面上项目Ⅰ型脊髓灰质炎病毒在新疆维吾尔自治区高免疫覆盖人群中传播内在机制的研究(项目批准号81373049)

摘　　要：目的分析四川省2009年Ⅱ型（Type 2）疫苗高变异脊髓灰质炎（脊灰）病毒[Vaccine High-mutant Poliovirus（PV）,VHMPVⅡ]的病毒学特征。方法对2009年5-6月从四川省泸州和成都市的2例急性弛缓性麻痹（Acute Flaccid Paralysis,AFP）病例中分离到的2株PVⅡ进行全基因组序列测定。结果全基因组序列测定结果显示,2株VHMPVⅡ全长7439个碱基（base pair,bp）,共编码2207个氨基酸。与赛宾（Sabin）Ⅱ型疫苗株病毒相比,2株VHMPVⅡ不存在bp的插入和缺失,VP1编码区核苷酸（nucleotide,nt）变异数分别为5个和7个,均属于VHMPVⅡ。2株病毒在VP1编码区共享5个nt变异,全长共享13个nt变异,提示已经发生了潜在流行。2株VHMPVⅡ均未发生型内或型间重组,在已知的2个减毒位点5＇非编码区nt481和VP1衣壳蛋白编码区nt2909位点上均发生回复突变。VP1编码区基因进化树分析表明,2株VHMPVⅡ处于同一传播链,该传播链病毒的进化独立于国内外至今发现的循环的Ⅱ型疫苗衍生脊灰病毒（Circulating Vaccine-derived）PV（c VDPVⅡ）,按照PV已知的基因进化速率估算该传播链已在人群中流行约260天。结论本研究结果表明,与VDPV类似,VHMPV同样可以在人群中发生流行,同时再次证明中国脊灰实验室网络监测具有高度的敏感性,能够及时发现VHMPV的传播,防止其衍变为cVDPV。Objective To evaluate the virological characters of type 2 vaccine high-mutant poliovirus （VHMPVII）. Method We conducted genomic sequence analysis to two strains of type 2 poliovirus ob- tained from 2 acute flaccid paralysis （AFP） patients of Luzhou and Chengdu, Sichuan province, between May and June, 2009. Result Genomic sequence analysis revealed that, these two strains had 7,439 ba- ses, encoding for 2,207 amino acids. Compared with the type 2 Sabin vaccine strain, the tested strains had 5 and 7 nucleic acids replaced in the VP1 coding region, which suggested that the 2 strains were high-mutant strains. Compared with each other, these two strains shared 13 nucleic acids substitution; 5of which were in the VP1 coding region, indicating potential for transmission. These two strains had 7,439 bases, encoding for 2,207 ami- no acids. Compared with the Sabin 2 vaccine strain, no insertion-deletion mutations were found. No genetic recombination was seen within or between genotype. A reverse mutation occurred at ntd81 of a non-coding region, and at nt2909 of the VP1 region; both are known as attenuated lo- ci. Phylogenetic analysis of the VP1 coding region showed that these 2 strains from Sichuan arose from the same transmission chain, whicfi has beenfound to exist in other type 2 VDPVs in other parts of the world. An estimate based on the poliovirus mu- tation rate showed that circulation had been going on for about 260 days. Conclusion This stud.y showed that, similar to VDPV strains, polioviruses with high genetic variation could circulate independently a- mong the population. The China polio laboratory network is very sensitive at detecting high mutant polio- virus promptly, so that further divergence and circulation can be prevented.

关 键 词：疫苗高变异脊髓灰质炎病毒 基因特征 潜在流行 

分 类 号：R512.4[医药卫生—内科学]