TRIM5 is an innate immune sensor for the retrovirus capsid lattice.
TRIM5 is an innate immune sensor for the retrovirus capsid lattice.
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DOI：
10.1038/nature09976
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发表时间：
2011-04-21
期刊：
影响因子：
64.8
通讯作者：
Luban, Jeremy
中科院分区：
文献类型：
--
作者：
Pertel, Thomas;Hausmann, Stephane;Morger, Damien;Zueger, Sara;Guerra, Jessica;Lascano, Josefina;Reinhard, Christian;Santoni, Federico A.;Uchil, Pradeep D.;Chatel, Laurence;Bisiaux, Aurelie;Albert, Matthew L.;Strambio-De-Castillia, Caterina;Mothes, Walther;Pizzato, Massimo;Gruetter, Markus G.;Luban, Jeremy
TRIM5是一种环状结构域-E3泛素连接酶，可在病毒侵入靶细胞胞浆后立即限制HIV-1和其他逆转录病毒的感染。抗病毒效力与TRIM5对逆转录病毒衣壳结构的亲和力相关，一些报道表明TRIM5在信号转导中发挥作用，但确切的限制机制尚不清楚。在这里，我们证明了TRIM5促进先天免疫信号，这种活性通过逆转录病毒感染和与衣壳晶格的相互作用而被放大。在异源二聚体泛素结合酶UBC13/UEV1a的作用下，TRIM5催化合成K63连接的独立泛素链，激活Tak1(MAP3K7)激酶复合体，刺激AP-1和NFκB信号传导。与HIV-1衣壳蛋白晶格的相互作用大大增强了TRIM5UBC13/UEV1a依赖的E3活性，逆转录病毒攻击诱导AP-1和NFκB依赖因子的转录，其幅度与TRIM5对入侵衣壳的亲和力相一致。最后，TAK1和UBC13/UEV1A参与了TRIM5对衣壳蛋白的特异性限制。因此，逆转录病毒限制因子TRIM5有两个与限制有关的额外活性：它结构性地促进先天性免疫信号，并作为逆转录病毒衣壳结构的模式识别受体。
TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by HIV-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm. Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice and several reports indicate that TRIM5 plays a role in signal transduction, but the precise mechanism of restriction is unknown. Here we demonstrate that TRIM5 promotes innate immune signaling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13/UEV1A, TRIM5 catalyzes the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (MAP3K7) kinase complex and stimulate AP-1 and NFκB signaling. Interaction with the HIV-1 capsid lattice greatly enhances the UBC13/UEV1A-dependent E3 activity of TRIM5 and challenge with retroviruses induces the transcription of AP-1 and NFκB-dependent factors with a magnitude that tracks with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13/UEV1A contribute to capsid-specific restriction by TRIM5. Thus, the retroviral restriction factor TRIM5 has two additional activities that are linked to restriction: it constitutively promotes innate immune signaling and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice.
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影响因子：
64.5
作者：
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DOI：
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影响因子：
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影响因子：
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作者：
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