HIV-1 B’亚型病毒感染者辅助蛋白Vpr特异性细胞免疫应答

目的探讨HIV-1 B’亚型病毒感染者针对辅助蛋白Vpr的细胞免疫(CTL)反应特征及其与病毒复制控制的关系。方法利用检测IFN-γ分泌的ELISPOT方法,以覆盖HIV-1 B亚型Vpr蛋白全长的重叠肽段作为刺激抗原检测143例未接受抗病毒治疗的HIV-1 B’亚型病毒感染者针对Vpr蛋白的特异性细胞免疫反应,并分析其与病毒载量的关系。结果有16.8%的感染者可以产生针对Vpr蛋白的特异性CTL反应;能识别至少一条Vpr多肽的感染者的病毒载量低于不能识别Vpr多肽的感染者的病毒载量,差别有统计学意义(P=0.0191);对VPR-B-3多肽的识别与低病毒载量紧密相关,该多肽可能包含与Vpr蛋白的生物学功能相关的关键氨基酸位点;Vpr蛋白区多肽在人群中的识别水平的差异与其序列变异程度有关。结论Vpr蛋白特异性的CTL反应与宿主对病毒复制的控制具有一定的相关性,对Vpr蛋白区所包含的CTL表位进行鉴定并探讨其在感染过程中的作用,可为HIV疫苗设计提供参考依据。

CTL responses directed against accessory protein Vpr in HIV-1 clade B' infected Individuals

Aim To investigate HIV-1 specific CTL responses directed against accessory protein Vpr and its impact on virus replication in HIV-1 clade B’ infected individuals.Methods 143 anti-retroviral therapy naive HIV-1 clade B’ infected subjects were assessed for HIV-1 specific CTL responses with an IFN‐γ Elispot assay by using overlapping peptides covering Vpr protein consensus sequence.Association between CTL responses and viral load was analysed.Results 16.8% of the study subjects recognized at least one overlapping Vpr peptide.Vpr-responsive subjects had lower plasma viral loads than that of non-responsive subjects,the difference is statistically significant（P=0.0191）;CTL recognition against OLP VPR-B-3 was correlated with low viral load suggesting that this peptide may contain amino acids critical for biological functions of Vpr protein.CTL responses against Vpr peptids in the study population were associated with Vpr sequence variation.Conclusion Vpr-specific CTL responses were correlated to the control of viral replication in the study population.Further characterization of the epitopes and their roles in pathogenesis of HIV-1 natural infection will benefit the design and testing of candidate vaccines