HIV-1毒株gag和pol基因区抗原表位及耐药性突变分析

Analyses on Antigen Epitopes and Drug Resistance Mutations of HIV-1 gag and pol Genes

通过研究HIV-1 gag和pol基因序列变异特征,以了解抗原表位变异特点和耐药性突变情况。采集HIV-1阳性全血样本,使用巢式PCR扩增gag和pol基因部分区段,得到23份样本的PCR序列和相应样本的克隆序列gag基因为449份、pol基因为402份,基因分型为HIV-1B和B′亚型。两种亚型的共享序列在选取的8个CTL抗原表位中,共有4个抗原表位发生了8个突变位点;另外位于p24区的5个抗原表位在PCR序列中没有发生变化,但在它们的克隆序列(9.80%)中发生了少数突变。在pol基因PCR序列和克隆序列中发现蛋白酶抑制剂(Protease inhibitors,PIs)和逆转录酶抑制剂(Reverse transcriptase inhibitors,RTIs)耐药性突变位点分别为18个和24个,其中只在克隆序列中发现的PIs和RTIs耐药性突变位点分别占其总数的94.44%(17/18)和62.50%(15/24)。结果显示本研究样本PCR序列中表现出耐药性的比例较高(17.39%),并在克隆序列中存在少数免疫逃逸和耐药性突变,提示部分样本对现行抗病毒药物产生一定程度的耐药。

To study the CTL antigen epitopes and drug resistance mutations of HIV-1 gag and pol genes through analyzing gag and pol gene sequences. The HIV-1 gag and pol gene fragments were amplified using nested polymerase chain reaction. A total of 23 PCR sequences, 449 cloned gag sequences and 402 cloned pol sequences were obtained. Sequence analyses showed the 23 samples were subtype B or Bt. A to- tal of 4 in 8 CTL antigen epitopes appeared 8 mutations in consensus sequence of subtype B and Br. There were no mutations found in the PCR sequences, whereas a few mutations were found in clone sequences （9.80%）in 5 antigen epitopes in p24 region. Eighteen PIs-related mutations and 24 RTIs-related mutations were found in PCR sequences and clone sequences in pol gene region, in which 17 （94.44%） PIs-related mutations and 15 （62.50%） RTIs-related mutations were found only in the clone sequences, respectively. The results showed that the prevalence of HIV-1 drug resistance strains in this study was at a higher level （17.39%）, suggesting that some samples were resistant to existing antiviral drugs.