Gene expression and viral prodution in latently infected, resting CD4+ T cells in viremic versus aviremic HIV-infected individuals
Gene expression and viral prodution in latently infected, resting CD4+ T cells in viremic versus aviremic HIV-infected individuals
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DOI：
10.1073/pnas.0437640100
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发表时间：
2003-02-18
影响因子：
11.1
通讯作者：
Fauci, AS
中科院分区：
文献类型：
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作者：
Chun, TW;Justement, JS;Fauci, AS
HIV-1存在于潜伏感染的静息CD 4（+）T细胞中已在感染个体中得到明确证实;然而，病毒表达的程度和HIV-1在该病毒库中持续存在的潜在机制尚未完全阐明。在这里，我们发现，大多数病毒血症患者的静息CD 4（+）T细胞能够在体外自发产生无细胞HIV-1。在存在细胞增殖和病毒复制抑制剂的情况下，静息CD 4（+）T细胞释放的HIV-1水平没有显著降低。然而，尽管HIV-1前病毒DNA和细胞相关的HIV-1 RNA水平与病毒血症患者相当，但大多数病毒血症患者的静息CD 4（+）T细胞不能产生病毒体。DNA微阵列分析表明，与病毒血症患者相比，病毒血症患者静息CD 4（+）T细胞中涉及转录调控、RNA加工和修饰以及蛋白质运输和囊泡运输的许多基因显著上调。这些结果表明，活跃的病毒复制对受感染的病毒血症患者的静息CD 4（+）T细胞的生理状态有显著影响，反过来，允许在没有外源性激活刺激的情况下释放HIV-1。此外，尽管存在细胞相关的HIV-1 RNA，但大多数病毒血症患者的潜伏病毒库并没有产生可定量的病毒体，因此，在有效治疗期间，病毒血症患者静息CD 4（+）T细胞中HIV-1 RNA转录的证据不一定被视为病毒复制持续的直接证据。
The presence of HIV-1 in latently infected, resting CD4(+) T cells has been clearly demonstrated in infected individuals; however, the extent of viral expression and the underlying mechanisms of the persistence of HIV-1 in this viral reservoir have not been fully delineated. Here, we show that resting CD4(+) T cells from the majority of viremic patients are capable of producing cell-free HIV-1 spontaneously ex vivo. The levels of HIV-1 released by resting CD4(+) T cells were not significantly reduced in the presence of inhibitors of cellular proliferation and viral replication. However, resting CD4(+) T cells from the majority of aviremic patients failed to produce virions, despite levels of HIV-1 proviral DNA and cell-associated HIV-1 RNA comparable to viremic patients. The DNA microarray analysis demonstrated that a number of genes involving transcription regulation, RNA processing and modification, and protein trafficking and vesicle transport were significantly upregulated in resting CD4(+) T cells of viremic patients compared to those of aviremic patients. These results suggest that active viral replication has a significant impact on the physiologic state of resting CD4(+) T cells in infected viremic patients and, in turn, allows release of HIV-1 without exogenous activation stimuli. In addition, given that no quantifiable virions were produced by the latent viral reservoir in the majority of aviremic patients despite the presence of cell-associated HIV-1 RNA, evidence for transcription of HIV-1 RNA in resting CD4(+) T cells of aviremic patients should not necessarily be taken as direct evidence for ongoing viral replication during effective therapy.