Evidence for gene expression by unintegrated human immunodeficiency virus type 1 DNA species

Evidence for gene expression by unintegrated human immunodeficiency virus type 1 DNA species
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DOI:
10.1128/jvi.78.20.11263-11271.2004
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发表时间:
2004-10-01
影响因子:
5.4
通讯作者:
Sonigo, P
Sonigo, P
中科院分区:
医学2区
文献类型:
--
作者:
Brussel, A;Sonigo, P

文献摘要

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人类免疫缺陷病毒1型(HIV-1) DNA的整合形式通常被认为是病毒基因表达的唯一模板。然而,一些研究表明,未整合的病毒DNA物种也可能支持转录。为了确定不同种类的HIV-1 DNA对病毒表达的贡献,我们首先在单轮感染试验中监测了细胞内各种HIV-1 DNA和RNA种类的水平。我们观察到,与HIV-1 DNA合成的早熟相比,病毒表达延迟,这表明只有持续足够时间的HIV-1 DNA物种才能有效转录。我们接下来评估了带有两个长末端重复序列的环状HIV-1 DNA的转录活性,因为据报道这些片段表现出内在的分子稳定性。我们的研究结果支持这样一种观点,即这些环状的HIV-1 DNA在HIV-1感染期间自然转录,从而参与病毒复制。
The integrated form of human immunodeficiency virus type 1 (HIV-1) DNA is classically considered to be the sole template for viral gene expression. However, several studies have suggested that unintegrated viral DNA species could also support transcription. To determine the contribution of the different species of HIV-1 DNA to viral expression, we first monitored intracellular levels of various HIV-1 DNA and RNA species in a single-round infection assay. We observed that, in comparison to the precocity of HIV-1 DNA synthesis, viral expression was delayed, suggesting that only the HIV-1 DNA species that persist for a sufficient period of time would be transcribed efficiently. We next evaluated the transcriptional activity of the circular forms of HIV-1 DNA bearing two long terminal repeats, since these episomes were reported to exhibit an intrinsic molecular stability. Our results support the notion that these circular species of HIV-1 DNA are naturally transcribed during HIV-1 infection, thereby participating in virus replication.