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为探讨2013年引起中国大陆麻疹复发的麻疹野病毒中和抗原血凝素(Hemagglutinin,HA)的变异动态,本研究对1993~2013年中国大陆流行的麻疹病毒H1基因型血凝素(HA)编码基因和氨基酸变异进行系统分析,为评价中国疫苗对2013年流行的麻疹野病毒的保护效果提供科学依据。选取2013年8株麻疹病毒代表株,扩增HA基因编码区序列(1 854bp)并进行序列测定和分析。从GenBank上下载45株1993~2012年中国流行株、中国疫苗株上海191(S-191)和长春47(C-47)和24株WHO参考株HA基因编码区序列,MEGA5.05构建亲缘关系树和进行氨基酸位点比对,分析重要中和抗原位点的变异。使用BioEdit进行同源性关系分析。根据HA基因序列的亲缘性关系分析,2013年麻疹病毒代表株均位于H1a亚型的第3分支,且2000年以后分离的H1a亚型的麻疹野毒株均属于该分支;8株2013年麻疹病毒代表株核苷酸和氨基酸的同源性分别为97.6%~99.8%和97.8%~100.0%,与1993~2012年H1a基因亚型麻疹病毒的核苷酸和氨基酸同源性分别为97.6%~99.6%和97.0%~99.6%,与中国疫苗株S-191和C-47的核苷酸和氨基酸同源性分别为94.3%~94.7%和94.6%~95.4%;与中国疫苗株S-191原型野病毒氨基酸序列比对,1993~2013年麻疹病毒代表株HA主要中和抗原位点未发生重大变异,但包括2013年代表株的近年流行的H1a麻疹毒株在氨基酸第240位由丝氨酸突变成了天冬酰胺(Ser240Asn),导致潜在的糖基化位点NLS238~240的缺失,但H1基因型麻疹病毒均保留有4个潜在的糖基化位点。中国大陆流行的麻疹病毒H1基因型在重要的中和抗原位点均保持稳定,中国使用的麻疹疫苗对中国现流行的麻疹病毒H1a亚型具有较好的保护效果。中国应继续加强流行麻疹病毒血凝素基因的动态监测,以评价我国疫苗对流行麻疹野病毒的保护效果,为我国消除麻疹提供疫苗使用的科学依据。
In order to explore the variation of Hemagglutinin (HA), the measles virus neutralizing antigen (HA) that caused the recurrence of measles in mainland China in 2013, this study analyzed the genetic variation of hemagglutinin (HA) Encoding gene and amino acid variation were systematically analyzed to provide a scientific basis for evaluating the protective effect of Chinese vaccines on the wild measles virus of 2013. Eight representative strains of measles virus in 2013 were selected to amplify the HA gene coding region sequence (1 854 bp) and sequenced and analyzed. Forty-five Chinese endemic strains from 1993 to 2012 were downloaded from GenBank. The HA gene coding sequences of Chinese vaccine strains Shanghai 191 (S-191) and Changchun 47 (C-47) and 24 WHO reference strains were downloaded from GenBank. MEGA5.05 Trees and amino acid site alignment, analysis of major neutralizing antigen site variation. Homology analysis using BioEdit. According to the phylogenetic analysis of the HA gene sequences, the representative strains of measles virus were all located on the third branch of the H1a subtype in 2013, and all the H1a subtypes of measles virus isolates isolated after 2000 belonged to this branch. Eight isolates of measles The nucleotide and amino acid homology of the representative strain of the virus was 97.6% -99.8% and 97.8% -100.0%, respectively. The nucleotide and amino acid homologies of the H1a subtype measles virus from 1993 to 2012 were 97.6% ~ 99.6% and 97.0% ~ 99.6%, respectively. The nucleotide and amino acid homologies with Chinese vaccine strains S-191 and C-47 were 94.3% ~ 94.7% and 94.6% ~ 95.4% 191 wild-type wild virus amino acid sequence alignment, from 1993 to 2013 measles virus representative strain HA main neutralizing antigen site did not occur significant changes, but in recent years, including the representative strains of H1a measles strains of recent years in the amino acid 240 position by the serine Mutated to asparagine (Ser240Asn), resulting in the deletion of the potential glycosylation site NLS238-240, but the H1 herpesvirus retained four potential glycosylation sites. The prevalence of measles virus H1 genotypes in mainland China remained stable at major neutralizing antigen sites. The measles vaccine used in China had a good protective effect on the H1N1 subtype currently circulating in China. China should continue to strengthen the dynamic monitoring of the hemagglutinin gene of measles virus to evaluate the protective effect of our country’s vaccine on wild measles virus and provide the scientific basis for the vaccine use in eliminating measles in China.