Unstimulated primary CD4+ T cells from HIV-1-positive elite suppressors are fully susceptible to HIV-1 entry and productive infection.
Unstimulated primary CD4+ T cells from HIV-1-positive elite suppressors are fully susceptible to HIV-1 entry and productive infection.
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来自 HIV-1 阳性精英抑制因子的未刺激的初级 CD4 T 细胞完全容易受到 HIV-1 的进入和生产性感染。
DOI：
10.1128/jvi.01721-10
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发表时间：
2011
影响因子：
5.4
通讯作者：
Blankson,JoelN
中科院分区：
文献类型：
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作者：
Rabi,SAlireza;O'Connell,KarenA;Nikolaeva,Daria;Bailey,JustinR;Jilek,BenjaminL;Shen,Lin;Page,KathleenR;Siliciano,RobertF;Blankson,JoelN
精英控制者或抑制者（ES）是一组HIV-1感染者，他们多年来保持病毒载量低于商业检测试剂的检测限。负责这种显着控制的机制正在进行深入研究，希望开发出有效对抗HIV-1的治疗性疫苗。在这项研究中，我们解决了问题的内在易感性ES CD 4 +T细胞感染。虽然我们和其他人先前已经表明ES的CD 4 +T细胞可以在体外被HIV-1分离株感染，但这些研究受到感染前CD 4 +T细胞的外源性激活和体外培养的混淆。为了避免与这种外源性激活相关的趋化因子受体表达的变化，我们在从ES、病毒血症患者和未感染供体的外周血中分离后直接感染纯化的CD 4 +T细胞。我们利用一种表达绿色荧光蛋白（GFP）的前病毒构建体，用趋CCR 5或趋CXCR 4的包膜假型化，使用基于荧光共振能量转移的单轮病毒-细胞融合测定来比较病毒进入。还通过评估GFP表达来比较生产性感染的频率。来自ES的CD 4 +T细胞与来自病毒血症患者和未感染供体的细胞一样或更容易受到HIV-1进入和产生性感染的影响。这项生理学研究的结果强烈表明，HIV-1进入和感染CD 4 +T细胞的差异不能单独解释病毒复制的精英控制。
Elite controllers or suppressors (ES) are a group of HIV-1-infected individuals who maintain viral loads below the limit of detection of commercial assays for many years. The mechanisms responsible for this remarkable control are under intense study, with the hope of developing therapeutic vaccines effective against HIV-1. In this study, we addressed the question of the intrinsic susceptibility of ES CD4+T cells to infection. While we and others have previously shown that CD4+T cells from ES can be infected by HIV-1 isolatesin vitro, these studies were confounded by exogenous activation andin vitroculture of CD4+T cells prior to infection. In order to avoid the changes in chemokine receptor expression that have been associated with such exogenous activation, we infected purified CD4+T cells directly after isolation from the peripheral blood of ES, viremic patients, and uninfected donors. We utilized a green fluorescent protein (GFP)-expressing proviral construct pseudotyped with CCR5-tropic or CXCR4-tropic envelope to compare viral entry using a fluorescence resonance energy transfer-based, single-round virus-cell fusion assay. The frequency of productive infection was also compared by assessing GFP expression. CD4+T cells from ES were as susceptible as or more susceptible than cells from viremic patients and uninfected donors to HIV-1 entry and productive infection. The results of this physiological study strongly suggest that differences in HIV-1 entry and infection of CD4+T cells alone cannot explain the elite control of viral replication.