Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1
Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1
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DOI：
10.1128/jvi.76.16.8276-8284.2002
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发表时间：
2002-08-01
影响因子：
5.4
通讯作者：
Kaslow, RA
中科院分区：
文献类型：
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作者：
Tang, JM;Tang, SH;Kaslow, RA
慢性人类免疫缺陷病毒1型（HIV-1）感染期间病毒RNA浓度（病毒载量[VL]）的设定点反映了与CD 8（+）细胞毒性T淋巴细胞（CTL）应答密切相关的病毒-宿主平衡，其严重依赖于人主要组织相容性复合体（MHC）的抗原呈递（即，HLA）I类分子。赞比亚-UAB HIV研究项目（ZUHRP）中259名主要为C分支病毒感染者（137名女性和122名男性）的HIV-1 VL差异与几种HLA I类等位基因和单倍型相关。特别是，一般的线性模型分析显示，在HLA等位基因B*57的受试者中，对数（10）VL较低（P = 0.002 [未校正]）先前与良好应答有关，并且在HLA B*39和A*30-Cw*03患者中（P = 0.002至0.016）;相同的分析还表明A*02-Cw*16、A*23-B*14和A*23-Cw*07个体的log（10）VL较高（P = 0.010至0.033）。这些HLA效应在调整年龄、性别和感染持续时间后仍然很强（P = 0.0002至0.075），并在VL类别的三个顺序中持续存在（P = 0.001至0.084）。相反，B*35（n = 15）和B*53（n = 53）都没有表现出明显的劣势，如其他地方报道的这些密切相关的等位基因。其他HLA与异常高（A*68、B*41、B*45和Cw*16）或低（B*13、Cw*12和Cw*18）VL的关联要么不稳定，要么反映了它们与其他I类变体的不平衡的紧密连锁。在多变量模型和替代分析中保留的三种一致有利的HLA I类变体存在于30.9%的VL最低（100，000）的受试者中。根据病毒血症水平，HLA谱的明显差异分布表明，在HIV-1感染期间，宿主对免疫控制和逃逸模式的遗传贡献很大。
The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8(+) cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log(10) VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log(10) VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.