Human immunodeficiency virus (HIV-1) infection selectively downregulates PD-1 expression in infected cells and protects the cells from early apoptosis in vitro and in vivo.
Human immunodeficiency virus (HIV-1) infection selectively downregulates PD-1 expression in infected cells and protects the cells from early apoptosis in vitro and in vivo.
复制标题
人类免疫缺陷病毒 (HIV-1) 感染选择性下调受感染细胞中的 PD-1 表达，并在体外和体内保护细胞免于早期凋亡。
DOI：
10.1016/j.virol.2008.03.015
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Ayyavoo,Velpandi
中科院分区：
文献类型：
--
作者：
Venkatachari,NarasimhanJ;Buchanan,WilliamG;Ayyavoo,Velpandi
程序性死亡-1(PD-1)是T细胞共刺激分子中的一员，在慢性病毒感染过程中在抗原特异性T细胞上高水平表达，而PD-1在HIV-1感染的CD4+T细胞中的表达尚不清楚。在这里，我们报告了被高效感染的CD4+T细胞丢失PD-1，而旁观者细胞不受影响。此外，在相同的感染环境中，p24+/PD-1阴性细胞比旁观者细胞更不容易发生凋亡。在体内也观察到了类似的结果，因为从HIV-1+个体分离的受感染T细胞的PD-1水平非常低，并且观察到的PD-1在体内的丢失与病毒载量、CD4计数和/或抗病毒治疗无关。综上所述，这些结果表明，生产性感染细胞通过下调PD-1来抵抗早期凋亡，而PD-1增强了效应T细胞对凋亡的敏感性，这表明PD-1在HIV-1感染中具有双重作用。
Programmed Death-1 (PD-1), a member of T cell costimulatory molecules is expressed in high levels on antigen specific T cells during chronic viral infection, whereas PD-1 expression in the context of HIV-1 infected CD4+ T cells is not known. Here we report that productively infected CD4+ T cells lose PD-1, whereas bystander cells were unaffected. Additionally, p24+/PD-1 negative cells are less susceptible to apoptosis compared to bystander cells in the same infected milieu. Similar results were observed in vivo, as infected T cells isolated from HIV-1+ individuals have significantly low level of PD-1 and the observed loss of PD-1 in vivo is independent of viral load, CD4 count, and/or antiviral treatment. Together these results indicate that productively infected cells are resistant to early apoptosis by downregulating PD-1, whereas PD-1 enhances the susceptibility of effector T cells to apoptosis suggesting a dual role for PD-1 during HIV-1 infection.