急性弛缓性麻痹病例中Ⅱ型脊髓灰质炎疫苗病毒变异株基因特征分析  

Genetic Characterization of TypeⅡ Vaccine Mutant Polioviruses Isolated from Acute Flaccid Paralysis (AFP) Cases

作　　者：李崇山[1] 张勇[1] 叶绪芳[2] 王海岩[3] 王东艳[1] 祝双利[1] 朱晖[1] 安洪秋[1] 李杰[1] 严冬梅[1] 许松涛[1] 毛乃颖[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,北京100050 [2]贵州省疾病预防控制中心,贵阳550004 [3]山东省疾病预防控制中心,济南250014

出　　处：《病毒学报》2007年第2期103-109,共7页Chinese Journal of Virology

基　　金：世界卫生组织(项目编号:WP/ICP/IVD/252/XC/048);卫生部2005~2006疾控专项经费

摘　　要：研究Ⅱ型脊髓灰质炎（脊灰）疫苗变异株的基因特征，为我国使用口服脊灰减毒活疫苗／脊灰灭活疫苗使用策略，维持无脊灰状态和全球最终消灭脊灰提供科学依据。根据型内鉴定的检测结果，从2000-2001年AFP病例分离到的Ⅱ型脊灰疫苗变异株中选取有聚集性的5株病毒进行全基因组序列测定（贵州省3株、山东省2株），并进行核苷酸、氨基酸同源性分析。贵州省3株病毒全基因组序列完全一致，但与SabinⅢ型病毒发生重组，重组区域在3A区（nt5343-5353）；与疫苗株相比，Ⅱ型区域变异10个碱基，其中VP1区变异4个，与SabinⅡ型株核苷酸同源性为99．56％，氨基酸同源性99．34％；Ⅲ型区域变异9个碱基。山东省2株病毒全基因序列共享16个突变位点，没有发生重组，与SabinⅡ型株相比，VP1区分别变异7个和4个碱基，核苷酸同源性分别为99．22％和99．56％，氨基酸同源性分别为99．0％和99．67％。上述5株病毒在重要的减毒位点nt481、nt2909均发生突变。此研究中5株病毒分属于两个不同的传播链，但是共享nt481、nt2909、nt2992三个突变位点，这3个突变位点不在重组区域内，他们的共同作用可能是影响病毒传播力的重要因素，但目前尚无证据证明脊灰疫苗病毒型间重组会增加病毒的毒力及传播力。The genetic characterization of vaccine mutant polioviruses isolated from AFP cases in China was analyzed for the purposes of offering scientific basis for the strategy of OPV/IPV administration and maintaining the polio-free status in China, as well as the polio eradication in the world. Based on the results of intratypic differential （ITD） test of all the vaccine-associated polioviruses isolated from AFP cases in 2000- 2001, the complete genome of 5 isolates （3 from Guizhou Province, 2 from Shandong Province） were sequenced to analyze the homology of nucleotide and amino acid sequences. Three isolates from Guizhou Province had completely the same nucleotide sequences, but recombined with Sabin Ⅲ in 3A region （nt5343-5353）. Compared with Sabin strains, 19 nucleotide substitutions were found, 10 in type Ⅱ region （4 of them in VP1 region）and 9 in typeⅢ region. The homology of nucleotide and amino acid sequences in VP1 region were 99.56% and 99.34% respectively as compared with that of Sabin Ⅱ. Two isolates from Shandong Province had no recombination and shared 16 nucleotide substitutions, seven and four nucleotide substitutions were found in their VP1 region respectively as compared with that of Sabin Ⅱ , and the homology of nucleotide and amino acid sequences were 99.22%-99.56% and 99.0%-99.67% respectively. Nucleotide substitutions were found at two important attenuation sites （nt481 and nt2909） in each of these 5 isolates. These 5 isolates were isolated from two transmission lineages, but they shared 3 nucleotide substitutions （nt481, nt2 909 and nt2 992）, which were not in recombination region. The co-action of these 3 substitutions may influence viral transmissibility. No evidence indicated that intertypic recombination of vaccine mutant polioviruses may enhance the viral neurovirulence and transmissibility.

关 键 词：脊髓灰质炎疫苗变异株 基因特征 序列测定和分析 

分 类 号：R373.2[医药卫生—病原生物学]