Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity
Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity
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DOI：
10.1073/pnas.071548198
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发表时间：
2001-04-24
影响因子：
11.1
通讯作者：
Goldfeld, AE
中科院分区：
文献类型：
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作者：
Flores-Villanueva, PO;Yunis, EJ;Goldfeld, AE
某些HLA-B抗原与艾滋病进展的缺乏有关。根据分子表位HLA-Bw 4和HLA-Bw 6的表达，HLA-B等位基因可分为两个相互排斥的组。值得注意的是，除了其在呈递用于免疫识别的病毒肽中的作用之外，HLA-Bw 4而不是HLA-Bw 6基序还作为自然杀伤细胞抑制性受体（KIR）的配体起作用。在这里，我们表明，深刻的抑制HIV-1病毒血症是显着相关的HLA-B等位基因，共享HLA-Bw 4表位的纯合性。此外，HLA-Bw 4等位基因的纯合性也与在具有明确定义的血清转化日期的第二组HIV-1感染个体中保持无AIDS和维持正常CD 4 T细胞计数的能力显著相关。这种关联与CC趋化因子受体5（CCR 5）中与HIV-1感染抗性相关的突变的存在无关，也与可能混淆结果的HLA等位基因的存在无关。我们的结论是HLA-Bw 4-轴承B等位基因的纯合性与一个显着的优势，HLA-Bw 4基序是重要的艾滋病发病机制。
Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA-B alleles can be divided into two mutually exclusive groups based on the expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to its role in presenting viral peptides for immune recognition, the HLA-Bw4, but not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is significantly associated with homozygosity for HLA-B alleles that share the HLA-Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly associated with the ability to remain AIDS free and to maintain a normal CD4 T cell count in a second cohort of HIV-l-infected individuals with well defined dates of seroconversion. This association was independent of the presence of a mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1 infection, and it was independent of the presence of HLA alleles that could potentially confound the results. We conclude that homozygosity for HLA-Bw4-bearing B alleles is associated with a significant advantage and that the HLA-Bw4 motif is important in AIDS pathogenesis.