| 金青青,冯燕,徐昌平,卢亦愚,钟淑玲,莫世华.浙江省1999—2011年麻疹流行株全基因组序列分析[J].Chinese journal of Epidemiology,2012,33(9):945-950 |
| 浙江省1999—2011年麻疹流行株全基因组序列分析 |
| Study on the genome sequence of measles viruses circulated in Zhejiang province during 1999 to 2011 |
| Received:May 28, 2012 |
| DOI：10.3760/cma.j.issn.0254-6450.2012.09.016 |
| KeyWord: 麻疹病毒 全基因组 疫苗 变异 |
| English Key Word: Measles virus Complete genome Vaccine Variation |
| FundProject:国家自然科学基金(30771903)；浙江省科技厅重大专项(2009C03011-4)；浙江省自然科学基金(Y2091178) |
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| Abstract: |
| 目的 从全基因组层面探讨浙汀省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及国外主西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，各基幽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。在核苷酸水甲上，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茼组的遗传距离(t=9.76，P<0.05；t=12.39，P结论 浙江麻疹流行株与疫曲株S191在各基因上均产生了较大的差异，现行疫苗株与H基凶型流行株之间的差异远大于疫苗株与国外优势流行株(D4，B3 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。 |
| English Abstract: |
| Objective To study the genetic variations between measles vaccine strain S191 and strains that circulated in Zhejiang province causing the epidemics during 1999 to 2011. 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 maior epidemic strains isolated in foreign countries. Results The homology of amino acid among the nine Zhejiang stains 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 gone, 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 Zhejiang epidemic atrains and vaccine strains was greater than the distances between epidemic strains of genotype D4, B3, and vaccine strains(t=-9.76, P<0.05; t=-12.39, P<0.05). Conclusion There were sightficant differences 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 diffcrences between the vaccine and the foreign epidemic strains (genotype D4, B3). Therefore, we should pay close attention to this trend, and to develop candidates for the development of vaccines, as early as possible. |
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