Trim5α accelerates degradation of cytosolic capsid associated with productive HIV-1 entry
Trim5α accelerates degradation of cytosolic capsid associated with productive HIV-1 entry
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DOI：
10.1074/jbc.m606066200
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发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Gallay, Philippe A.
中科院分区：
文献类型：
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作者：
Chatterji, Udayan;Bobardt, Michael D.;Gallay, Philippe A.
TRIM 5 α（三重基序5 α蛋白）已与人类免疫缺陷病毒1型（HIV-1）感染非人类细胞的跨物种限制有关，但其发生机制仍有待充分阐明。在这里，我们证明了HIV-1的衣壳（CA）蛋白在表达猴TRIM 5 α的细胞中比在表达人TRIM 5 α的细胞中降解得更快。由Gag和Pol编码的其他蛋白质不受TRIM 5 α介导的加速降解的影响。TRIM 5 α加速CA降解显然是通过非蛋白酶体途径发生的。TRIM 5 α选择性地加速CA群体的降解，其到达限制性细胞的胞质溶胶，但不加速CA群体的降解，其终止于囊泡隔室中。考虑到胞质CA代表“生产性”进入核心，而囊泡CA代表“非生产性”进入核心，我们的研究结果表明TRIM 5 α通过作用于进入的胞质CA来中断HIV-1的感染途径。病毒进入的模式不影响TRIM 5 α对胞质CA的加速降解。因此，这项研究揭示了TRIM 5 α介导的HIV-1限制与通常与病毒有效进入相关的细胞质CA选择性降解之间的相关性。
The TRIM5 alpha(tripartite motif 5 alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but the mechanism by which this occurs remains to be fully elucidated. Here we demonstrate that the capsid (CA) protein of HIV-1 is more rapidly degraded in cells expressing monkey TRIM5 alpha than in cells expressing humanTRIM5 alpha. Other proteins encoded by Gag and Pol are not subject to TRIM5 alpha-mediated accelerated degradation. The accelerated CA degradation by TRIM5 alpha apparently occurs via a nonproteosomal pathway. TRIM5 alpha selectively accelerates degradation of the CA population, which reached the cytosol of restrictive cells, but not the CA population, which ended into the vesicular compartment. Given that cytosolic CA represents "productively" entered cores, whereas vesicular CA represents "nonproductively" entered cores, our findings suggest that TRIM5 alpha interrupts the infectious pathway of HIV-1 by acting on the incoming cytosolic CA. The mode of viral entry does not influence the accelerated degradation of cytosolic CA by TRIM5 alpha. Thus, this study reveals a correlation between TRIM5 alpha-mediated HIV-1 restriction and a selective degradation of cytosolic CA normally associated with productive viral entry.