Revisiting HIV-1 uncoating.
Revisiting HIV-1 uncoating.
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DOI：
10.1186/1742-4690-7-96
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发表时间：
2010-11-17
期刊：
影响因子：
3.3
通讯作者：
Arhel N
中科院分区：
文献类型：
--
作者：
Arhel N
HIV脱衣被定义为在病毒基因组进入细胞核之前，在被感染细胞的细胞质内发生的病毒衣壳的脱落。它是HIV-1早期感染的必经步骤，伴随着发生逆转录的逆转录复合物（rtc）和整合前复合物（PICs）之间的过渡，后者能够整合到宿主基因组中。对HIV-1剥壳的性质和时间的研究充满了困难，特别是由于衣壳组装容易受到实验操作的影响。然而，最近对衣壳结构、逆转录病毒限制和核输入机制的研究，以及最近全基因组研究和细胞成像方法的技术进步，已经大大改变了我们对HIV脱膜的理解。尽管早期的研究表明，在病毒进入细胞后立即发生脱衣，因此在感染细胞中衣壳的作用微不足道，但最近的数据表明，脱衣在几个小时后发生，并且衣壳在其感染的细胞中具有非常重要的作用：向细胞核运输，反转录和核输入。了解到脱壳发生在较晚的阶段，表明病毒衣壳在运输到细胞核的过程中与细胞骨架和其他细胞质组分广泛相互作用，这导致我们对确定HIV治疗的潜在治疗靶点的努力进行了相当大的重新评估。这篇综述讨论了我们目前对HIV脱包膜的理解，传染性和及时脱包膜之间的功能相互作用，以及揭示合适的方法来研究脱包膜和解决许多尚未解决的问题。
HIV uncoating is defined as the loss of viral capsid that occurs within the cytoplasm of infected cells before entry of the viral genome into the nucleus. It is an obligatory step of HIV-1 early infection and accompanies the transition between reverse transcription complexes (RTCs), in which reverse transcription occurs, and pre-integration complexes (PICs), which are competent to integrate into the host genome. The study of the nature and timing of HIV-1 uncoating has been paved with difficulties, particularly as a result of the vulnerability of the capsid assembly to experimental manipulation. Nevertheless, recent studies of capsid structure, retroviral restriction and mechanisms of nuclear import, as well as the recent expansion of technical advances in genome-wide studies and cell imagery approaches, have substantially changed our understanding of HIV uncoating. Although early work suggested that uncoating occurs immediately following viral entry in the cell, thus attributing a trivial role for the capsid in infected cells, recent data suggest that uncoating occurs several hours later and that capsid has an all-important role in the cell that it infects: for transport towards the nucleus, reverse transcription and nuclear import. Knowing that uncoating occurs at a later stage suggests that the viral capsid interacts extensively with the cytoskeleton and other cytoplasmic components during its transport to the nucleus, which leads to a considerable reassessment of our efforts to identify potential therapeutic targets for HIV therapy. This review discusses our current understanding of HIV uncoating, the functional interplay between infectivity and timely uncoating, as well as exposing the appropriate methods to study uncoating and addressing the many questions that remain unanswered.
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DOI：
10.1073/pnas.90.13.6125
发表时间：
1993-07-01
影响因子：
11.1
作者：
BUKRINSKY, MI;SHAROVA, N;STEVENSON, M
通讯作者：
STEVENSON, M
影响因子：
5.4
作者：
Black, Lesa R.;Aiken, Christopher
通讯作者：
Aiken, Christopher
影响因子：
3.7
作者：
Auewarakul, P;Wacharapornin, P;Puthavathana, P
通讯作者：
Puthavathana, P
影响因子：
3.3
作者：
Arhel, Nathalie J.;Souquere-Besse, Sylvie;Charneau, Pierre
通讯作者：
Charneau, Pierre
影响因子：
10.5
作者：
BOWERMAN, B;BROWN, PO;VARMUS, HE
通讯作者：
VARMUS, HE