麻疹疫苗株S-191全基因序列测定及与流行株进化关系的初步研究  

Sequencing of measles virus vaccine strain Shanghai-191 genome and comparative analysis of nudeotide sequences between vaccine strain and wild-type strains in China

作　　者：于洁[1] 王海龙[1] 陈实[1] 张靖[1] 张卿[1] 靳玉琴[1] 李启明[1] 

机构地区：[1]北京生物制品研究所基因工程研究室,100024

出　　处：《中华微生物学和免疫学杂志》2008年第7期624-628,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的对国内现在使用的Shanghai-191（S-191）疫苗株进行全基因组测序，针对国内已经分离出的毒株，分析它们与疫苗株的核酸序列差异以及流行特征。方法利用RT-PCR的方法分段扩增S-191疫苗株的全基因并测序，从GenBank中获得全球24条麻疹全基因序列和211株中国各省分离到的麻疹流行株以及WHO各基因型参考株的N基因C端456个核苷酸序列，计算麻疹序列13个编码区和非编码区的突变率，分析病毒株和疫苗株基因型和遗传距离，构建基因亲缘性关系树。结果获得S-191疫苗株的全基因序列并递交GenBank收录，进化树分析表明大部分流行株为H1基因型。各省流行株与S-191相比遗传距离为6．7％～8．2％。突变率分析显示非编码区的突变率明显高于编码区，编码区中N基因的突变率最大。结论本研究表明，中国大陆的麻疹病毒流行株以H1基因型为主，不存在明显的地域流行差异，在时间上也没有明显的突变积累特征。S-191疫苗株与近年来的麻疹流行株在遗传距离上差异较大，其保护作用需做进一步追踪探讨。Objective To explore the distinction between measles vaccine strain Shanghai-191 （S-191） and wild-type strains in China at molecular level. Methods After having been amplified by RT-PCR, the nucleotides of S-191 was sequenced and analyzed with reference to the sequences obtained from GenBank, which includes 24 whole genome sequences, 211 sequences of wild-type strains isolated from China and WHO reference strains. Results The sequence of S-191 strain had been submitted to GenBank. Phylogenetic analysis of the COOH terminal 456 nucleotides coding for the nucleoprotein （N） indicated that most of the measles virus strains from China were members of clade HI. The genetic distances between the virus strains detected in a number of provinces and S-191 strain were 6.7% -8.2%. It is noteworthy that the mutation rate of non-coding regions was considerably higher than that of coding regions. The mutation rate of N gene was the highest among all of the coding regions. Conclusion This report shows that genotype H1 is widely distributed throughout the country. The circulation has no apparent geographic and temporal restriction. The evolution of measles virus should be closely followed.

关 键 词：麻疹病毒 RT-PCR 序列分析 Shanghai-191 

分 类 号：R392[医药卫生—免疫学]