HIV-1 genome nuclear import is mediated by a central DNA flap
HIV-1 genome nuclear import is mediated by a central DNA flap
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DOI：
10.1016/s0092-8674(00)80828-4
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发表时间：
2000-04-14
期刊：
影响因子：
64.5
通讯作者：
Charneau, P
中科院分区：
文献类型：
--
作者：
Zennou, V;Petit, C;Charneau, P
HIV-1 和其他慢病毒在逆转录病毒中具有在非分裂细胞中复制的独特特性。这一特性依赖于核输入途径的使用，使病毒 DNA 能够穿过宿主细胞的核膜。在HIV-1逆转录中，正链合成的中心起始和终止连续的中心链置换事件产生正链重叠：中心DNA瓣。我们在这里展示了中央 DNA 瓣作为 HIV-1 DNA 核输入的 cia 决定因素。野生型病毒线性 DNA 几乎完全导入细胞核，并在细胞核中整合或环化。相比之下，缺乏 DNA 瓣的突变病毒 DNA 在受感染细胞中作为未整合的线性 DNA 积聚在核膜附近。一致地，缺乏 DNA 瓣的 HIV-1 载体表现出强烈的核输入缺陷，可以通过重新插入 DNA 瓣序列将其纠正到野生型水平。
HIV-1 and other lentiviruses have the unique property among retroviruses to replicate in nondividing cells. This property relies on the use of a nuclear import pathway enabling the viral DNA to cross the nuclear membrane of the host cell. In HIV-1 reverse transcription, a central strand displacement event consecutive to central initiation and termination of plus strand synthesis creates a plus strand overlap: the central DNA flap. We show here that the central DNA flap acts as a cia-determinant of HIV-1 DNA nuclear import. Wildtype viral linear DNA is almost entirely imported into the nucleus where it integrates or circularizes. In contrast, mutant viral DNA, which lacks the DNA flap, accumulates in infected cells as unintegrated linear DNA, at the vicinity of the nuclear membrane. Consistently, HIV-1 vectors devoid of DNA flap exhibit a strong defect of nuclear import, which can be corrected to wild-type levels by reinsertion of the DNA flap sequence.