风疹病毒疫苗株BRD-Ⅱ全基因组分析

Genome-wide association study of rubella virus vaccine strain BRD-

  • 摘要:
    目的 进行风疹病毒疫苗株BRD-Ⅱ全基因组分析,旨在掌握该基因组的序列特征。
    方法 采用二代测序的方法对BRD-Ⅱ疫苗株进行全基因组测序,采用最大似然法分析该基因组与部分疫苗株及野生型风疹病毒株的亲缘性关系树;测定各疫苗株蛋白的核酸序列平均遗传距离及对各风疹疫苗株结构蛋白进行同源性比对,还对该基因组与AY258323.1基因组序列进行比对,分析野生型风疹病毒参考毒株与BRD-Ⅱ疫苗株E1蛋白同源性。
    结果 BRD-Ⅱ株是单分子单股正链核糖核酸(RNA),由9 778个核苷酸组成,GC含量为69.35%, C蛋白由300个氨基酸组成,E2糖蛋白由282个氨基酸组成,E1糖蛋白由481个氨基酸组成。结果显示,各蛋白的核酸序列平均遗传距离分别为P150蛋白0.066 700、P90蛋白0.061 933、C蛋白0.057 850、E2蛋白0.068 167、E1蛋白0.068 833;通过比对,2株BRD-Ⅱ株的E2蛋白和E1蛋白区域氨基酸序列并未发生改变,证实了E1蛋白的保守区域。
    结论 明确该基因组的序列特征,并为后续开展主要抗原基因的遗传稳定性检测奠定了基础。

     

    Abstract:
    Objective To perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome.
    Methods Second-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ.
    Results The sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison.
    Conclusion The sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.

     

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