急性弛缓性麻痹聚集病例病原毒力和分子特征分析  

Analysis of the Molecular Characterization and Neurovirulence of the Isolates from the Clustered AFP Cases in China

作　　者：陈立[1] 张礼璧[1] 赵蓉[1] 张勇[1] 祝双利[1] 王东艳[1] 安洪秋[1] 朱晖[1] 侯晓辉[1] 严冬梅[1] 秦明晖[2] 清水博之 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国家脊髓灰质炎实验室 [2]四川省疾病预防控制中心,成都610031 [3]日本国立感染症研究所

出　　处：《病毒学报》2006年第6期421-425,共5页Chinese Journal of Virology

基　　金：卫生部疾病预防控制专项(2003年)日本JICA扩大免疫合作项目(2003/2004年)

摘　　要：为探索脊灰病毒型内重组、位点突变等分子特征与神经毒力的关系,对2002年6月四川省攀枝花地区发生的急性弛缓性麻痹(acute flaccid paralysis,AFP)聚集病例的分离病毒株进行了转基因小鼠(PVR-Tg21 mice)神经毒力实验和全基因组核苷酸序列测定。结果显示:所测4株分离病毒(均为Ⅱ型脊灰病毒)神经毒力没有明显升高。4株病毒基因全长都是7 439bp,编码区翻译的氨基酸全长2 207aa。4株病毒的VP1区核苷酸序列完全相同。6208和6235c两株病毒是由Ⅱ型和Ⅲ型脊灰病毒在3A区重组而来,6209和6236两株病毒是由Ⅱ型和Ⅰ型脊灰病毒在2C区重组而来。4株病毒在5'非编码区nt481和VP1区的nt2 909两个强减毒位点都发生回复突变,6209和6236两株病毒重组的SabinⅠ的重要减毒位点nt6 203亦发生回复突变。结合神经毒力实验和序列分析结果可以确定脊灰病毒的型别间的重组与神经毒力没有直接关系,同时可以推论SabinⅢ的nt5 832,SabinⅡ的nt1 450和nt2 386这3个位点可能是毒力相关位点。There occurred the clustered acute flaccid paralysis （AFP） cases in Panzhihua city of Sichuan Province in June, 2002. Three virus strains （6208, 6209, 6236） were isolated from three AFP cases and three strains （6233c, 6234c, 6235c） from their contacts. Neurovirulence assay were performed on four of the six isolates （6208, 6209, 6236, 6235c） using transgenic mice （PVR-Tg21 mice）, and their complete genomic sequences were determined. The complete genomic sequences showed the isolates were vaccine-recombinant polioviruses （VRPV）, and there were reverse mutations at some important attenuated sites, and also substitutions at some other sites. The neurovirulence of the four isolates did not change significantly as compared with Sabin Ⅱ . The results demonstrate the neurovirulence of polioviruses does not relate to recombination within different serotypes of polioviruses. The deduction is that the three sites （nt5 832 Of SabinⅢ ,nt1l 450 and nt2 386 of SabinⅡ ） are proposal relative sites to neurovirulence.

关 键 词：神经毒力 疫苗重组脊髓灰质炎病毒 全基因组序列分析 AFP聚集病例 

分 类 号：R373.2[医药卫生—病原生物学]