中国脊髓灰质炎病毒疫苗株基因特征及其神经毒力的初步观察  

GENETIC VARIATIONS OF VACCINE POLIOVIRUS ISOLATES IN CHINA AND THEIR RELATION TO NEUROVIRULENCE

作　　者：李杰[1,2] 米山彻夫[1,2] 张礼壁[1,2] 侯晓辉 郑红[1,2] 方勇 原稔[1,2] 荻原昭夫 

机构地区：[1]中国预防医学科学院病毒学研究所国家脊髓灰质炎实验室 [2]日本国立预防卫生研究所病毒第二部肠道室

出　　处：《病毒学报》1997年第3期208-214,共7页Chinese Journal of Virology

基　　金：卫生部科研基金;国家自然科学基金;日本国际协力事业团polio项目

摘　　要：中国脊髓灰质炎（脊灰）病毒疫苗株普遍存在基因变异的现象，如重组、点突变等〔１〕。我们选出１０株有代表性的变异株，在具有人脊灰病毒受体基因的转基因小鼠ＰＶＲ－Ｔｇ２１〔２〕中做毒力分析，发现Ｓａｂｉｎ１基因型（ＶＰ１）与野毒基因型（３Ｄ）的重组株显示很强的神经毒力，其ＰＤ５０ｉｎＴＣＩＤ５０（简称ＰＤ５０）值为４．５，而Ｓａｂｉｎ１标准株的ＰＤ５０值大于８．０。另外两株Ⅰ型疫苗株只在关键性核苷酸位点发生突变，只在位点５２５－Ｕ发生突变的一株，其ＰＤ５０值为５．０，另一株在位点４８０－Ｇ及２７９５－Ａ突变，其ＰＤ５０值为５．８，均显示较强的神经毒力。一株Ｓａｂｉｎ２基因型（ＶＰ１）与Ｓａｂｉｎ３基因型（３Ｄ）的重组株，其神经毒力（ＰＤ５０≥５．９）亦明显高于Ｓａｂｉｎ２标准株（ＰＤ５０＞７．５）；而１株Ｓａｂｉｎ２基因型（ＶＰ１）与（Ｓａｂｉｎ１＋Ｓａｂｉｎ２）基因型（３Ｄ）重组株的神经毒力（ＰＤ５０＝７．５０）无明显提高。对Ⅲ型疫苗株的神经毒力分析发现，１株Ｓａｂｉｎ３基因型（ＶＰ１）与Ｎｏｎ－Ｓａｂｉｎ基因型（３Ｄ）重组株的神经毒力，高于仅在核苷酸位点４７２－Ｕ突变的一株疫苗株。值得提出的是，另一株Ⅲ型疫苗?Genetic variations,such as recombination,point mutation,have generally occurred in vaccine polioviruses isolated in China.10 representative variants were selected,and their neurovirulence were examined in the transgenic mice(PVR-Tg21) carrying the human poliovirus receptor.The data showed that the neurovirulence of two recombinants that were Sabin 1 type genome in VP1 coding region recombined with wild type genome in 3D polymerase coding region was very strong,the PD 50 in TCID 50 (PD 50 ) of the mutants were 4.5,while the PD 50 of Sabin 1 reference strain was greater than 8.0.The other two type 1 vaccine strains were only carrying the point mutations in critical nucleotides,one of them carried the mutation in 525-U,its PD 50 was 5.0,the other carried the mutations in 480-G and 2795-A,its PD 50 was 5.8.Both of them had stronger neurovirulence.The neurovirulence of a recombinant (PD 50 >5.9) which was Sabin 2 type genome in VP1 recombined with Sabin 3 type genome in 3D was stronger than that of Sabin 2 reference strain(PD 50 >7.5),but the recombinant which was Sabin 2 type genome in VP1 recombined with(Sabin 1+Sabin 2)type genome in 3D was not neurovirulent.Among three type 3 vaccine strains,a recombinant which was Sabin 3 type genome in VP1 recombined with non-Sabin type genome in 3D had neurovirulence stronger than that of a type 3 vaccine strain only carrying a mutation in 472-U.It’s notable that neurovirulence of another type 3 vaccine strain carrying an additional mutation at 2637-C besides 472-U,was very strong (PD 50 <4.8),even stronger than that of the type 3 wild strain(PD 50 <5.8),up to now,it has not been reported,that the 2637-C position is critical for neuroviulence.The data presented here suggested that the intermolecular recombination,possibly in connection with mutation may be the mechanism in the loss of attenuation of vaccine polioviruses.

关 键 词：脊髓灰质炎病毒疫苗株 基因特征 神经毒力 

分 类 号：R373.22[医药卫生—病原生物学] R392－33[医药卫生—基础医学]