Jin Qing-qing, Feng Yan, Xu Chang-ping, Lu Yi-yu, Zhong Shu-ling, Mo Shi-hua
Medical School of Ningbo University, Ningbo 315211, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2012 Sep;33(9):945-50.
To study the genetic variations between measles vaccine strain S191 and strains that circulated in Zhejiang province causing the epidemics during 1999 to 2011.
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.
The homology of amino acid among the nine Zhejiang 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 gene, 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 strains and vaccine strains was greater than the distances between epidemic strains of genotype D(4), B(3) and vaccine strains (t = -9.76, P < 0.05; t = -12.39, P < 0.05).
There were significant 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 genotype epidemic strains were much larger than the differences between the vaccine and the foreign epidemic strains (genotype D(4), B(3)). Therefore, we should pay close attention to this trend, and to develop candidates for the development of vaccines, as early as possible.
研究麻疹疫苗株S191与1999年至2011年期间在浙江省引起疫情流行的毒株之间的基因变异情况。
采用逆转录聚合酶链反应（RT-PCR）法扩增9株浙江麻疹毒株的全序列。对产物进行测序，并将获得的序列与疫苗株S191及国外分离的主要流行毒株进行比对和分析。
9株浙江毒株之间氨基酸同源性为98.77% - 99.89%。这些毒株未受正向选择影响，各基因变异仍处于随机漂移状态。与疫苗株S191相比，浙江麻疹病毒有135至159个氨基酸变化，其中113个位点为共同可变位点，导致5个糖基化位点发生突变。在核苷酸水平上，浙江毒株与疫苗株S191之间差异最大的是N基因，平均分歧率为5.5%，而在氨基酸水平上差异最大的是P蛋白，平均突变率为7.7%。此外，根据全基因组序列，浙江流行毒株与疫苗株之间的遗传距离大于D(4)基因型、B(3)基因型流行毒株与疫苗株之间的距离（t = -9.76，P < 0.05；t = -12.39，P < 0.05）。
浙江流行毒株与疫苗株S191在各基因上均存在显著差异。当前疫苗株与H基因型流行毒株之间的差异远大于疫苗株与国外流行毒株（D(4)基因型、B(3)基因型）之间的差异。因此，应密切关注这一趋势，并尽早研发疫苗候选株。
