Grifoni Alba, Montesano Carla, Palma Paolo, Giovanetti Marta, Castelli-Gattinara Guido, Ciccozzi Massimo, Mattei Maurizio, Mancino Giorgio, Salerno Alfredo, Colizzi Vittorio, Amicosante Massimo
Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
Immunology. 2014 Dec;143(4):631-9. doi: 10.1111/imm.12344.
Viral and host factors can influence HIV-1 progression, among them human leucocyte antigen (HLA) has shown the strongest effect. However, studies on the functional contribution of HLA in controlling HIV progression toward AIDS are limited by multiple issues, including the viral strain variability within the study subjects. In this study, in a cohort of children infected with a monophyletic strain (CRF02_AG) during an outbreak, we evaluated the HIV-1 Gag, Vif, Vpr, Tat and hepatitis C virus E1/E2 (as control) proteins circulating in a cohort for the capability to be presented by the HLA molecules in the same population. A total of 70 Non-progressors and 37 Progressors to AIDS were evaluated. In the presence of a constant capability of HIV-1 to mutate in the region containing epitopes of Gag protein, the number of epitopes recognized in silico by the combination of the HLA alleles along the Gag consensus sequence is significantly higher in the Non-progressors compared with Progressors (HLA-A: Non-progressors = 1.532 ± 1.211, Progressors = 0.7714 ± 1.031, P = 0.0016; HLA-B: Non-progressors = 1.556 ± 1.298, Progressors = 1.000 ± 0.817, P = 0.0319; HLA-DR: Non-progressors = 13.30 ± 9.488, Progressors = 7.294 ± 6.952, P = 0.0006). Similar results were obtained for the other HIV-1 proteins Vif and Vpr, whereas no differences were obtained in the number of epitopes for the hepatitis C virus E1/E2 protein sequence or for the scrambled HIV-1 sequence. Finally, the results were confirmed also in a subgroup of subjects where both HLA typing and Gag sequence were available. In conclusion, in the absence of bias due to viral strain diversity, it is the overall fitting of the HLA molecules that are capable of better binding HIV-1 proteins in determining the major role in the control of HIV-1 replication and progression to AIDS.
病毒和宿主因素可影响HIV-1的病程进展，其中人类白细胞抗原（HLA）的影响最为显著。然而，关于HLA在控制HIV向艾滋病进展过程中的功能作用的研究受到诸多问题的限制，包括研究对象体内病毒株的变异性。在本研究中，我们对一组在一次疫情期间感染单一毒株（CRF02_AG）的儿童进行了研究，评估了该队列中循环的HIV-1 Gag、Vif、Vpr、Tat蛋白以及丙型肝炎病毒E1/E2蛋白（作为对照）被同一人群中的HLA分子呈递的能力。共评估了70名病情未进展者和37名进展为艾滋病者。在HIV-1在包含Gag蛋白表位的区域发生突变的能力恒定的情况下，与进展为艾滋病者相比，病情未进展者中沿着Gag共有序列的HLA等位基因组合在计算机模拟中识别的表位数量显著更多（HLA-A：病情未进展者 = 1.532 ± 1.211，进展为艾滋病者 = 0.7714 ± 1.031，P = 0.0016；HLA-B：病情未进展者 = 1.556 ± 1.298，进展为艾滋病者 = 1.000 ± 0.817，P = 0.0319；HLA-DR：病情未进展者 = 13.30 ± 9.488，进展为艾滋病者 = 7.294 ± 6.952，P = 0.0006）。对于其他HIV-1蛋白Vif和Vpr也获得了类似结果，而丙型肝炎病毒E1/E2蛋白序列或HIV-1随机序列的表位数量则没有差异。最后，在一个同时具备HLA分型和Gag序列的受试者亚组中也证实了这些结果。总之，在不存在病毒株多样性偏差的情况下，能够更好结合HIV-1蛋白的HLA分子的整体适配性在决定控制HIV-1复制和向艾滋病进展中起主要作用。
