HIV-1B’/C重组病毒感染者Vif、Vpr和Vpu特异性细胞免疫应答研究

CTL responses directed against accessory proteins in HIV-1 B'/C recombinant infected Chinese

目的探讨我国HIV-1B’/C重组病毒感染者针对HIV-1调节蛋白的细胞免疫反应特征及其与病毒复制控制的关系。方法以覆盖HIV-1C亚型Vpr、Vpu和Vif蛋白全长的重叠肽段作为刺激抗原,利用ELISPOT方法检测新疆HIV-1B’/C重组病毒感染者的特异性细胞免疫反应。使用SIGMAPLOT10.0和SIGMASTAT3.5进行统计分析,用双尾t检验比较组间差异,用Spearmam秩相关分析免疫反应与病毒载量及CD4细胞计数的关系。结果在检测的60名HIV-1B’/C重组病毒感染者中,能够识别Vif、Vpr和Vpu蛋白产生CTL应答者分别为68%、52%和8%,Vpr和Vif蛋白存在多个强CTL反应的免疫优势区域。研究中还发现针对Vpr、Vif和Vpu蛋白的CTL反应强度和广度与HIV感染者的病毒载量及CD4细胞数量无明显的相关性。结论HIV-1Vpr和Vif蛋白包含多个可被机体免疫系统特异性T细胞识别的免疫优势区域。对这些免疫优势区所包含的CTL表位进行鉴定并探讨其在自然感染过程中的作用,对新一代的HIV疫苗设计有重要的参考意义。

Objective To characterize HIV-1-specific CTL responses directed against accessory proteins and investigate its correlation with the control of virus replication in HIV-1 B'/C recombinant infected Chinese. Methods HIV-1-specific CTL responses were analyzed with an IFN-γ ELISPOT assay by using overlapping peptides spanning HIV-1 Clade C Vpr,Vpu and Vif proteins consensus sequences. Statistical analysis and graphical presentation were done using SIGMAPLOT 10.0 and SIGMASTAT 3.5. Statistical analysis of significance (P values) was based on two-tailed t tests where the significance threshold was P<0.05. Results Vpr and Vif were recognized in 52% and 68% of the tested individuals,respectively,while HIV-1 Vpu was rarely targeted by CTL in infected individuals (8%). And multiple immunodominant regions were detected in Vpr and Vif proteins. No significant correlation was observed between the magnitude and breadth of CTL responses directed against accessory proteins and the control of virus replication in this study. Conclusion Vpr and Vif served as targets for HIV-1-specific CTL contain multiple immunodominant regions. Further characterization of the epitopes and their roles in pathogenesis of HIV-1 natural infection will benefit the design and testing of candidate vaccines.