Factors that mold the nuclear landscape of HIV-1 integration.

Factors that mold the nuclear landscape of HIV-1 integration.
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塑造HIV-1整合的核景观的因素。

DOI:
10.1093/nar/gkaa1207
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发表时间:
2021-01-25
影响因子:
14.9
通讯作者:
Engelman AN
Engelman AN
中科院分区:
生物学2区
文献类型:
--
作者:
Bedwell GJ;Engelman AN

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逆转录病毒逆转录本整合到它们感染的细胞染色质中是病毒复制所必需的。逆转录病毒整合具有深远的后果,从使致命的人类疾病永久化到塑造后生动物的进化。慢病毒人类免疫缺陷病毒1型(HIV-1)是艾滋病大流行的病原体,由于其整合前复合体(PIC)的活跃核输入,可以有效地感染间期细胞。为了实现整合,PIC必须在密集的核环境中导航,在这种环境中,基因组被组织成不同的染色质状态,根据细胞的需要具有不同的可及性。HIV-1衣壳蛋白与特定的宿主因子相互作用,促进PIC核输入,而病毒整合酶(负责病毒DNA整合的酶)与细胞核蛋白和核苷酸碱基的额外相互作用引导整合到特定的染色体位置。HIV-1整合有利于转录活性染色质,如斑点相关结构域,而不利于异染色质,包括板层相关结构域。在这篇综述中,我们描述了促进HIV-1 PIC核导入和整合位点靶向的病毒-宿主相互作用,强调了参与这两个步骤的因素之间的共性。此外,我们还讨论了核环境如何影响HIV-1整合部位的选择以及主动和潜在病毒感染的建立。
The integration of retroviral reverse transcripts into the chromatin of the cells that they infect is required for virus replication. Retroviral integration has far-reaching consequences, from perpetuating deadly human diseases to molding metazoan evolution. The lentivirus human immunodeficiency virus 1 (HIV-1), which is the causative agent of the AIDS pandemic, efficiently infects interphase cells due to the active nuclear import of its preintegration complex (PIC). To enable integration, the PIC must navigate the densely-packed nuclear environment where the genome is organized into different chromatin states of varying accessibility in accordance with cellular needs. The HIV-1 capsid protein interacts with specific host factors to facilitate PIC nuclear import, while additional interactions of viral integrase, the enzyme responsible for viral DNA integration, with cellular nuclear proteins and nucleobases guide integration to specific chromosomal sites. HIV-1 integration favors transcriptionally active chromatin such as speckle-associated domains and disfavors heterochromatin including lamina-associated domains. In this review, we describe virus-host interactions that facilitate HIV-1 PIC nuclear import and integration site targeting, highlighting commonalities among factors that participate in both of these steps. We moreover discuss how the nuclear landscape influences HIV-1 integration site selection as well as the establishment of active versus latent virus infection.
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