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目的研究我国人免疫缺陷病毒1型(HIV-1)B’亚型主要流行株在宿主免疫压力下的基因变异及抗原表位的变化特征,探讨选择压力、基因离散率和抗原表位变化之间的关系。方法从确诊的HIV-1感染并的全血样本中提取基因组DNA,经套式聚合酶链反应(PCR)扩增后,将扩增产物进行纯化和测序。然后将所得序列进行系统进化树和氨基酸变异分析,使用GCG软件包的Distance程序对P17和P24两个区段计算基因距离,用Diverge程序计算同义替换(Ks)和非同义替换(Ka)及二者之间的比值,并对我国人群中较常见的HLA型别限制的CTL表位的突变情况进行分析。结果HIV-1 B’亚型毒株的P17区段的Ks/Ka值<1,而P24区段的Ks/Ka值>1;P24部分的基因离散率低于P17部分;P17区段抗原表位的保守率为34.94%,而P24区段抗原表位的保守率为67.38%;从基因离散率、所受的选择压力及抗原表位的突变率3个方面来看,HIV-1的P17区段均明显大于P24区段。结论HIV-1 B’亚型毒株的P17区段的抗原表位变化较大,而P24区段的抗原表位相对较为保守。提示P24区段的CTL表位更适合于表位疫苗的研制。
Objective To study the genetic variation and antigenic epitopes of major subtype of HIV-1 B 'subtype of HIV-1 in China, and to explore the influence of selection pressure, gene dispersion rate and antigen epitope variation Relationship between. Methods Genomic DNA was extracted from whole blood samples of confirmed HIV-1 infection. After amplification by nested polymerase chain reaction (PCR), the amplified products were purified and sequenced. Then phylogenetic tree and amino acid variation analysis were performed on the obtained sequences. Distance was calculated using the Distance program of the GCG software package for both P17 and P24 segments, and synonymous substitutions (Ks) and non-synonymous substitutions (Ka) were calculated using the Diverge program And the ratio between the two, and the more common in our population of HLA-restricted CTL epitope mutations were analyzed. Results The Ks / Ka value of P17 segment of HIV-1 B 'subtype strain was <1, while the Ks / Ka value of P24 segment was> 1; the genetic divergence rate of P24 segment was lower than that of P17 segment; The conservative rate was 34.94%, while the P24 segment epitope was conserved at 67.38%. From the aspects of gene dispersal rate, selection pressure and the mutation rate of antigen epitopes, HIV-1 P17 The sections were significantly larger than the P24 section. Conclusion The epitopes of P17 in HIV-1 B 'subtype strains vary greatly, while the epitopes in P24 are relatively conservative. Tip CTL epitope P24 section is more suitable for the development of epitope vaccine.