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标签:HIV-1 病毒 基因
摘要 : “1-型人免疫缺陷病毒” (HIV-1)的感染需要将病毒基因组整合到寄主DNA中,该病毒已知会优先整合到一个子类的转录活性基因中。Mauro Giacca及同事在这篇论文中报告说,核位置影响目标基因的选择。

“1-型人免疫缺陷病毒” (HIV-1)的感染需要将病毒基因组整合到寄主DNA中,该病毒已知会优先整合到一个子类的转录活性基因中。Mauro Giacca及同事在这篇论文中报告说,核位置影响目标基因的选择。他们发现,被该病毒优先作为目标的热点,在细胞核中最靠近核孔的外壳中比在中心位置更普遍,这说明,也许由于HIV-1整合酶的半衰期较短,该病毒会与它在进入细胞核途中所碰到的第一批开放染色质区域发生相互作用。


Nuclear architecture dictates HIV-1 integration site selection


Long-standing evidence indicates that human immunodeficiency virus type 1 (HIV-1) preferentially integrates into a subset of transcriptionally active genes of the host cell genome1, 2, 3, 4. However, the reason why the virus selects only certain genes among all transcriptionally active regions in a target cell remains largely unknown. Here we show that HIV-1 integration occurs in the outer shell of the nucleus in close correspondence with the nuclear pore. This region contains a series of cellular genes, which are preferentially targeted by the virus, and characterized by the presence of active transcription chromatin marks before viral infection. In contrast, the virus strongly disfavours the heterochromatic regions in the nuclear lamin-associated domains5 and other transcriptionally active regions located centrally in the nucleus. Functional viral integrase and the presence of the cellular Nup153 and LEDGF/p75 integration cofactors are indispensable for the peripheral integration of the virus. once integrated at the nuclear pore, the HIV-1 DNA makes contact with various nucleoporins; this association takes part in the transcriptional regulation of the viral genome. These results indicate that nuclear topography is an essential determinant of the HIV-1 life cycle.

来源: Nature 浏览次数:0


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