Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo
Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo
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DOI：
10.1128/jvi.77.13.7383-7392.2003
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发表时间：
2003-07-01
影响因子：
5.4
通讯作者：
Siliciano, RF
中科院分区：
文献类型：
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作者：
Hermankova, M;Siliciano, JD;Siliciano, RF
在人类免疫缺陷病毒 1 型 (HIV-1) 感染个体中，即使在长期接受高活性抗逆转录病毒治疗 (HAART) 治疗的患者中，携带潜伏整合原病毒的静息记忆 CD4(+) T 淋巴细胞的小型储存库仍然存在。这种病毒库使抗逆转录病毒药物根除 HIV-1 感染的前景变得更加复杂。因此，了解 HIV-1 潜伏期是如何建立和维持的至关重要。特别是，确定是否涉及转录或转录后机制非常重要。因此，我们对长期HAART患者外周血中高度纯化的静息CD4(+) T淋巴细胞群体中的HIV-1 DNA和mRNA进行了测量。在此类患者中，持续性 HIV-1 的主要形式是潜伏整合原病毒。通常，每 10(6) 个静息 CD4(+) T 细胞可检测到 100 个 HIV-1 DNA 分子。使用能够检测单分子RNA标准品的逆转录酶PCR检测仅检测到非常低水平的未剪接HIV-1 RNA（类似于50个拷贝/10(6)静息CD4(+)T细胞）。多重剪接的 HIV-1 RNA 水平低于检测限（
In individuals with human immunodeficiency virus type 1 (HIV-1) infection, a small reservoir of resting memory CD4(+) T lymphocytes carrying latent, integrated provirus persists even in patients treated for prolonged periods with highly active antiretroviral therapy (HAART). This reservoir greatly complicates the prospects for eradicating HIV-1 infection with antiretroviral drugs. Therefore, it is critical to understand how HIV-1 latency is established and maintained. In particular, it is important to determine whether transcriptional or posttranscriptional mechanisms are involved. Therefore, HIV-1 DNA and mRNAs were measured in highly purified populations of resting CD4(+) T lymphocytes from the peripheral blood of patients on long-term HAART. In such patients, the predominant form of persistent HIV-1 is latent integrated provirus. Typically, 100 HIV-1 DNA molecules were detected per 10(6) resting CD4(+) T cells. Only very low levels of unspliced HIV-1 RNA (similar to50 copies/10(6) resting CD4(+) T cells) were detected using a reverse transcriptase PCR assay capable of detecting a single molecule of RNA standard. Levels of multiply spliced HIV-1 RNA were below the limit of detection (