Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression
Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression
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DOI：
10.1128/jvi.79.20.12674-12680.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Telenti, A
中科院分区：
文献类型：
--
作者：
Bleiber, G;May, M;Telenti, A
人类对人类免疫缺陷病毒1型（HIV-1）的易感性存在很大差异。我们评估了参与病毒生命周期的9个宿主基因的变体在调节HIV-1感染中的作用。离体评估等位基因对来自健康献血者的纯化的CD 4 T细胞中的病毒复制的影响（n = 128）。此后，候选等位基因进行了评估，在体内队列的HIV-1感染者（n = 851）没有接受有效的抗逆转录病毒治疗。作为基准测试，我们测试了12个先前报道的影响HIV-1感染的宿主遗传变异以及9个候选基因中的单核苷酸多态性。这导致PML、TSG 101和PP 1A的三个等位基因与HIV-1疾病进展的差异可能相关。在考虑新基因变体和先前报道的基因变体的综合影响的模型中，我们估计它们的影响可能导致从500个CD 4 T细胞/μ l到< 200个CD 4 T细胞/μ l的时间延长或缩短长达2.8年。
Humans differ substantially with respect to susceptibility to human immunodeficiency virus type 1 (HIV-1). We evaluated variants of nine host genes participating in the viral life cycle for their role in modulating HIV-1 infection. Alleles were assessed ex vivo for their impact on viral replication in purified CD4 T cells from healthy blood donors (n = 128). Thereafter, candidate alleles were assessed in vivo in a cohort of HIV-1-infected individuals (n = 851) not receiving potent antiretroviral therapy. As a benchmark test, we tested 12 previously reported host genetic variants influencing HIV-1 infection as well as single nucleotide polymorphisms in the nine candidate genes. This led to the proposition of three allelles of PML, TSG101, and PP1A as potentially associated with differences in progression of HIV-1 disease. In a model considering the combined effects of new and previously reported gene variants, we estimated that their effect might be responsible for lengthening or shortening by up to 2.8 years the period from 500 CD4 T cells/mu l to < 200 CD4 T cells/mu l.