Long-Term Control of HIV-1 in Hemophiliacs Carrying Slow-Progressing Allele HLA-B*5101
Long-Term Control of HIV-1 in Hemophiliacs Carrying Slow-Progressing Allele HLA-B*5101
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DOI：
10.1128/jvi.00171-10
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
Takiguchi, Masafumi
中科院分区：
文献类型：
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作者：
Kawashima, Yuka;Kuse, Nozomi;Takiguchi, Masafumi
据报道，HLA-B*51等位基因与艾滋病的缓慢进展有关，但这种关联的机制尚不清楚。在本研究中，我们分析了HLA-B*5101对1985年以前感染HIV-1的日本血友病患者临床结果的影响，这些患者于1998年被招募参加本研究。HLA-B*5101（+）血友病表现出明显缓慢的进展。对10例抗逆转录病毒治疗（ART）无HLA-B*5101（+）血友病患者的4个HLA-B*限制性表位的hiv -1特异性细胞毒性T淋巴细胞（CTL）应答分析表明，pol283 -8特异性CD8(+) T细胞的频率与病毒载量呈负相关，而其他3个表位特异性CD8(+) T细胞的频率与病毒载量呈正相关。控制HIV-1复制约25年的HLA-B*5101（+）血友病患者的HIV-1具有野生型Pol283-8序列或Pol283-8V突变，这不会严重影响t细胞识别，而其他HLA-B*5101（+）血友病患者的HIV-1具有该表位的逃逸突变。结果表明，在HLA-B*5101阳性血友病患者中，HIV-1在大约25年内的控制与pol283 -8特异性CD8(+) t细胞应答有关，而HIV-1缺乏控制与pol283 -8特异性逃逸突变体的出现有关。
HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101(+) hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101(+) hemophiliacs showed that the frequency of Pol283-8-specific CD8(+) T cells was inversely correlated with the viral load, whereas the frequencies of CD8(+) T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101(+) hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101(+) hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8(+) T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants.