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.
出处
《病毒学报》
CAS
CSCD
北大核心
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
