CAJ | 학술논문

目的从全基因组层面探讨浙江省1999-2011年麻疹病毒的变异及其与疫苗株S191之间的差异.方法选取浙江省不同年份分离的麻疹病毒流行株9株,采用RT-PCR方法扩增全基因组序列,并与疫苗株S191及国外主要流行基因型毒株进行全序列比较分析.结果 1999-2011年浙江麻疹流行株间的氨基酸同源性为98.77％～ 99.89％,麻疹病毒尚未受到明显的正向压力,各基因的变异仍属随机漂移.与疫苗株S191相比,两者间氨基酸的同源性仅为96.63％～ 98.16％,分别存在135～159个氨基酸的改变,其中共同的氨基酸变异位点113个,导致5个糖基化位点的变异.在核苷酸水平上,N基因的平均变异率最大(5.5％)；而在氨基酸水平上,P蛋白的平均变异率最大(7.7％).此外,在全基因组序列上,浙江流行株与各国疫苗株的遗传距离均大于D4、B3基因型流行株与各国疫苗组的遗传距离(t=9.76,P＜0.05；t=-12.39,P＜0.05).结论浙江麻疹流行株与疫苗株S 191在各基因上均产生了较大的差异,现行疫苗株与H基因型流行株之间的差异远大于疫苗株与国外优势流行株(D4、B(1)基因型)之间的差异,应密切关注这一变化趋势,及早研究后备麻疹免疫株.
목적 종전기인조층면탐토절강성1999-2011년마진병독적변이급기여역묘주S191지간적차이.방법 선취절강성불동년빈분리적마진병독류행주9주,채용RT-PCR방법확증전기인조서렬,병여역묘주S191급국외주요류행기인형독주진행전서렬비교분석.결과 1999-2011년절강마진류행주간적안기산동원성위98.77％～ 99.89％,마진병독상미수도명현적정향압력,각기인적변이잉속수궤표이.여역묘주S191상비,량자간안기산적동원성부위96.63％～ 98.16％,분별존재135～159개안기산적개변,기중공동적안기산변이위점113개,도치5개당기화위점적변이.재핵감산수평상,N기인적평균변이솔최대(5.5％)；이재안기산수평상,P단백적평균변이솔최대(7.7％).차외,재전기인조서렬상,절강류행주여각국역묘주적유전거리균대우D4、B3기인형류행주여각국역묘조적유전거리(t=9.76,P＜0.05；t=-12.39,P＜0.05).결론 절강마진류행주여역묘주S 191재각기인상균산생료교대적차이,현행역묘주여H기인형류행주지간적차이원대우역묘주여국외우세류행주(D4、B(1)기인형)지간적차이,응밀절관주저일변화추세,급조연구후비마진면역주.
Objective To study the genetic variations between measles vaccinc strain S191 and strains that circulated in Zhejiang province causing the epidemics during 1999 to 20 1 1.Methods Complete sequence of the nine Zhejiang measles strains were amplified by RT-PCR assay.Products were sequenced and the obtained sequences were aligned and analyzed with vaccine strains S191 and the major epidemic strains isolated in foreign countries.Results The homology of amino acid among the nine Zhcjiang strains were 98.77％-99.89％.The strains were not affected by positive selection and the variations on each gene were still in random drift.Compared to vaccine strain S191,there were 135 to 159 amino acid changes in Zhejiang measles virus,in which 113 points were common variable positions,resulting in mutations on five glycosylation sites.At the nucleotide level,the biggest differences between the Zhejiang strains and the vaccine strain S191 were found on N gcne,with the average divergent ratio as 5.5％,while the biggest one was P protein,in the amino acid level,with the average mutation rate as 7.7％.In addition,with the complete genome sequences,the genetic distance between Zhcjiang epidemic strains and vaccine strains was greater than the distances between epidenic strains of genotype D4,B3 and vaccine strains (t=-9.76,P＜0.05；t=-12.39,P＜0.05).Conclusion There were significant differcnccs found in the each of the genes between Zhejiang epidemic strains and the vaccine strain S191.The differences between the current vaccine strains and H genotypc epidemic strains were much larger than the differences between the vaccine and the forcign epidemic strains (genotype D4,B3).Therefore,wc should pay close attcntion to this trend,and to develop candidates for the dcvclopnent of vaccines,as early as possible.