HIV-1 extrachromosomal 2-LTR circular DNA is long-lived in human macrophages
HIV-1 extrachromosomal 2-LTR circular DNA is long-lived in human macrophages
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DOI：
10.1089/vim.2005.18.190
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发表时间：
2005-03-01
期刊：
影响因子：
2.2
通讯作者：
Klotman, ME
中科院分区：
文献类型：
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作者：
Gillim-Ross, L;Cara, A;Klotman, ME
HIV-1染色体外2-LTR环（cc 2LTR）在分裂的细胞群中迅速丢失，因此可能被解释为代表新的感染和正在进行的病毒复制。然而，最近的研究表明，cc 2LTR在感染的生长停滞的T细胞系中持续存在，超过了先前在分裂细胞群中确定的预测半衰期。在本研究中，对cc 2LTR稳定性的评价扩展至包括原代人巨噬细胞，一种HIV-1的天然非分裂靶标。通过定量实时PCR，发现在感染整合酶活性和整合酶缺陷型重组HIV-1的巨噬细胞中，cc 2LTR持续到感染后21天，而在活化的CD 4（+）T淋巴细胞中，它们随时间迅速下降。这种持续性与指示基因荧光素酶的持续低水平表达有关。这些数据表明，在接受抑制性HAART的HIV-1感染患者的PBMC中存在HIV-1 α 2LTR可能是由于新感染的分裂细胞的持续产生，或者是由于在非分裂细胞群体中持续存在环状物，其中环状物似乎是稳定的。此外，该细胞群中的染色体外环状DNA可能是持续病毒蛋白表达的来源。
HIV-1 extrachromosomal 2-LTR circles (cc2LTR) are rapidly lost in dividing cell populations and, therefore, might be interpreted as representing new infection and ongoing viral replication. However, recent work demonstrated that cc2LTR persist in infected, growth-arrested T cell lines beyond their predicted half-life as previously determined in dividing cell populations. In this study, the evaluation of the stability of cc2LTR was extended to include primary human macrophages, a natural, non-dividing target of HIV-1. By quantitative real-time PCR, cc2LTR were found to persist out to 21 days post-infection in macrophages infected with both integrase competent and integrase-defective, recombinant HIV-1, whereas in activated CD4(+) T lymphocytes, they rapidly decreased over time. This persistence was associated with persistent, low level expression of the indicator gene, luciferase. These data suggest that the presence of HIV-1 cc2LTR in the PBMC of HIV-1-infected patients on suppressive HAART could be due either to ongoing generation of newly infected dividing cells, or persistence of circles in non-dividing cell populations where they appear to be stable. Furthermore, exrachromosomal circular DNA in this cell population could be a source of persisent viral protein expression.