SARS-CoV毒株E、M、N和S基因分子变异研究

Molecular Evolution on E,M,N and S Genes of SARS-CoV Strains

目的通过对SARS-CoV毒株基因序列的变异分析,揭示SARS-CoV毒株出现和流行与基因进化的关系。方法对广东地区SARS-CoV毒株进行序列分析,其余毒株序列从GenBank检索,采用DNAstar5.0软件,对检索的SARS-CoV的E、M、N、S基因核苷酸序列进行比对和分析;并结合临床资料对变异毒株进行流行病学分析。结果以果子狸冠状病毒(SZ-3)为基准,102株人类毒株中,6株毒株E基因的4个氨基酸发生置换,两株毒株发生缺失变异;果子狸毒株M基因的第5位丝氨酸置换为人类毒株甘氨酸并减少1个糖蛋白位点,此外M基因有38株毒株发生8个氨基酸置换变异;6株毒株N基因发生氨基酸置换,3株毒株发生缺失变异;人类毒株S基因中9个氨基酸全部发生变异并增加1个糖蛋白位点,与果子狸毒株不同比例占0.72%(9/1255);部分毒株中S基因的27个氨基酸在发生置换变异,7株毒株发生缺失变异。结论冠状病毒S基因中9个氨基酸置换和1个糖蛋白位点影响,可能导致人类SARS-CoV毒株出现和SARS流行;SARS流行持续和传播扩大与S基因进化变异相一致。所以认为,SARS-CoV毒株S基因变异可能在SARS出现和流行中发挥极其重要的作用。

Objective To study the molecular evolution of SARS - CoY in the emergence and outbreak of SARS by means of analyzing the genetic variation of SARS - CoVs. Methods The genomes sequencing from SARS - CoV strains from Guangdong were detected and others were collected from GenBank, which were analyzed with DNAstar 5.0, compared with the differences in the E, M, N and E gene of SARS - CoVs. The epidemiological analysis was carried out by way of combining the clinical data. Results There were 102 SARS - CoVs from humans and 2 from HPC - CoV. As compared with HPC - CoV （SZ - 3）, 4 amino acids in E gene in 6 isolates were substituted and 2 isolates varied in deletion of nucleotide.The serine in situs 5 of M gene from HIE - CoVs was substituted with the glycine from entire SARS - CoVs, and 8 antino acid domains in M gene of 38 strains were substituted; those domains in 6 stains in N gene were substituted and 3 strains varied in deletion of nucleotide. Nine amino acids in S gene in entire human SARS - CoVs were substituted with flint from HPC- CoV with the ratio of 0.72% （9/1255） and one glycoprotein domain in No 227 amino acid increased in entire human SARS- CoVs .Twenty - seven amino acids in S gene in some human strains and 7 isolates varied in deletion of nucleotide. Conclusions Emergence and outbreak of SARS night possibly result from nine amino acid substitutions and one glycoprotein domain impact on S gene of SARS - CoVs and the further evolution of S gene is coincided with the SARS continuation and spreading. It suggests that the variation in S gene in SARS - CoV takes a very important role in emergence and outbreak of SARS.