Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5alpha.

Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5alpha.
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在恒河体限制HIV-1时,可视化蛋白酶体的中间体。

DOI:
10.1083/jcb.200706154
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发表时间:
2008-02-11
影响因子:
7.8
通讯作者:
Hope, Thomas J.
Hope, Thomas J.
中科院分区:
生物学1区
文献类型:
--
作者:
Campbell, Edward M.;Perez, Omar;Anderson, Jenny L.;Hope, Thomas J.

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TRIM 5蛋白构成一类限制因子,其防止宿主细胞被来自不同物种的逆转录病毒感染。TRIM 5 α在病毒进入后早期限制逆转录病毒感染,在病毒逆转录产物产生之前。然而,潜在的限制机制仍不清楚。在这项研究中,我们表明,在恒河猴TRIM 5 α(rhTRIM 5 α)介导的HIV-1感染的限制,细胞质HIV-1病毒复合物可以与TRIM 5 α蛋白的浓度称为胞浆体。我们观察到rhTRIM 5 α和细胞质HIV-1病毒复合物之间的动态相互作用,包括病毒复合物周围rhTRIM 5 α胞质体样结构的从头形成。我们观察到,蛋白酶体抑制使HIV-1保持稳定地隔离在大的rhTRIM 5 α胞质体中,阻止HIV-1病毒复合物从胞质中清除,并揭示了限制过程中的中间体。此外,我们可以测量到在限制性酶切的这个中间步骤停止的病毒复合物中没有衣壳蛋白的损失,这表明任何rhTRIM 5 α介导的衣壳蛋白损失都需要蛋白酶体活性。
TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. TRIM5α restricts retroviral infection early after viral entry, before the generation of viral reverse transcription products. However, the underlying restriction mechanism remains unclear. In this study, we show that during rhesus macaque TRIM5α (rhTRIM5α)–mediated restriction of HIV-1 infection, cytoplasmic HIV-1 viral complexes can associate with concentrations of TRIM5α protein termed cytoplasmic bodies. We observe a dynamic interaction between rhTRIM5α and cytoplasmic HIV-1 viral complexes, including the de novo formation of rhTRIM5α cytoplasmic body–like structures around viral complexes. We observe that proteasome inhibition allows HIV-1 to remain stably sequestered into large rhTRIM5α cytoplasmic bodies, preventing the clearance of HIV-1 viral complexes from the cytoplasm and revealing an intermediate in the restriction process. Furthermore, we can measure no loss of capsid protein from viral complexes arrested at this intermediate step in restriction, suggesting that any rhTRIM5α-mediated loss of capsid protein requires proteasome activity.
DOI: 10.1091/mbc.e06-12-1075
发表时间: 2007-06-01
影响因子: 3.3
作者:
Campbell, Edward M.;Dodding, Mark P.;Hope, Thomas J.
通讯作者: Hope, Thomas J.
DOI: 10.1016/j.virol.2006.10.025
发表时间: 2007-04-10
期刊: VIROLOGY
影响因子: 3.7
作者:
Campbell, Edward M.;Perez, Omar;Hope, Thomas J.
通讯作者: Hope, Thomas J.
DOI: 10.1074/jbc.m606066200
发表时间: 2006-12-01
影响因子: 4.8
作者:
Chatterji, Udayan;Bobardt, Michael D.;Gallay, Philippe A.
通讯作者: Gallay, Philippe A.
DOI: 10.1073/pnas.0403364101
发表时间: 2004-08-10
影响因子: 11.1
作者:
Perron, MJ;Stremlau, M;Sodroski, J
通讯作者: Sodroski, J
DOI: 10.1073/pnas.200286297
发表时间: 2000-10-24
影响因子: 11.1
作者:
Towers, G;Bock, M;Danos, O
通讯作者: Danos, O