LINE-1 Retrotransposable Element DNA Accumulates in HIV-1-Infected Cells
LINE-1 Retrotransposable Element DNA Accumulates in HIV-1-Infected Cells
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DOI：
10.1128/jvi.02257-13
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发表时间：
2013-12-01
影响因子：
5.4
通讯作者：
Ostrowski, Mario A.
中科院分区：
文献类型：
--
作者：
Jones, R. Brad;Song, Haihan;Ostrowski, Mario A.
1型长散布核元件（L1）是自主逆转录转座元件，保留了人类基因组中的活性潜力，但受到宿主因素的抑制。将L1反转录转座到染色体DNA中可导致基因组不稳定性，而在胞质溶胶中反转录L1具有激活先天免疫传感器的潜力。我们假设HIV-1感染会损害L1元件的细胞控制，导致逆转录转座事件的诱导。在这里，我们表明，HIV-1感染增强L1逆转录病毒在Jurkat细胞中的Vif和Vpr依赖的方式。在原代CD 4（+）细胞中，HIV-1感染导致L1 DNA的积累，至少大部分是染色体外的。这些数据暴露了HIV-1和内源性逆转录转座因子之间未被识别的相互作用，这可能对HIV-1感染的先天免疫应答以及HIV-1诱导的基因组不稳定性和细胞病变性具有影响。
Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable elements that retain the potential for activity in the human genome but are suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription of L1 in the cytosol has the potential to activate innate immune sensors. We hypothesized that HIV-1 infection would compromise cellular control of L1 elements, resulting in the induction of retrotransposition events. Here, we show that HIV-1 infection enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent manner. In primary CD4(+) cells, HIV-1 infection results in the accumulation of L1 DNA, at least the majority of which is extrachromosomal. These data expose an unrecognized interaction between HIV-1 and endogenous retrotransposable elements, which may have implications for the innate immune response to HIV-1 infection, as well as for HIV-1-induced genomic instability and cytopathicity.