Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses.
Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses.
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DOI：
10.1016/j.chom.2012.10.007
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发表时间：
2012-11-15
影响因子：
30.3
通讯作者：
Neil SJ
中科院分区：
文献类型：
--
作者：
Galão RP;Le Tortorec A;Pickering S;Kueck T;Neil SJ
识别病原体特异性或异常位置分子基序的抗病毒蛋白完美地充当模式识别受体并向免疫系统发出信号。在这里，我们研究了干扰素诱导的病毒限制因子束缚蛋白 (CD317/BST2) 是否具有这样的信号传导作用，已知该因子通过将病毒粒子物理束缚到细胞表面来抑制 HIV-1 颗粒的释放。我们发现，在限制 Vpu 缺陷型 HIV-1 后，tetherin 可充当病毒传感器，诱导 NFκB 依赖性促炎基因表达。信号传导需要涉及病毒粒子保留的系链蛋白胞外结构域和细胞质尾部的决定簇，包括内吞基序，尽管信号传导独立于病毒粒子内吞作用。此外，TNF 受体相关因子 TRAF6 的募集和丝裂原激活蛋白激酶 TAK1 的激活对于信号传导至关重要。人类系绳蛋白介导有效信号传导的能力可能是由于原始人类与黑猩猩分化后发生的五个氨基酸缺失而产生的。 ► 人类 Tetherin 限制 HIV-1 释放，诱导 NFκB 依赖性基因表达 ► Tetherin 敏感的 HIV-1 突变体诱导增强的促炎细胞因子表达 ► 信号传导需要 Tetherin 的胞外结构域和细胞质尾部的决定簇 ► TAK1 激活和 TRAF6 募集对于 Tetherin 依赖性信号传导至关重要
Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal to the immune system. Here we investigated whether the interferon-induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit HIV-1 particle release by physically tethering virions to the cell surface, has such a signaling role. We find that upon restriction of Vpu-defective HIV-1, tetherin acts as a virus sensor to induce NFκB-dependent proinflammatory gene expression. Signaling requires both tetherin’s extracellular domain involved in virion retention and determinants in the cytoplasmic tail, including an endocytic motif, although signaling is independent of virion endocytosis. Furthermore, recruitment of the TNF-receptor-associated factor TRAF6 and activation of the mitogen-activated protein kinase TAK1 are critical for signaling. Human tetherin’s ability to mediate efficient signaling may have arisen as a result of a five amino acid deletion that occurred in hominids after their divergence from chimpanzees. ► Restriction of HIV-1 release by human tetherin induces NFκB-dependent gene expression ► Tetherin-sensitive HIV-1 mutants induce enhanced proinflammatory cytokine expression ► Signaling requires tetherin’s extracellular domain and determinants in the cytoplasmic tail ► TAK1 activation and TRAF6 recruitment are critical for tetherin-dependent signaling
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影响因子：
6.7
作者：
Casartelli N;Sourisseau M;Feldmann J;Guivel-Benhassine F;Mallet A;Marcelin AG;Guatelli J;Schwartz O
通讯作者：
Schwartz O
影响因子：
6.7
作者：
Janvier K;Pelchen-Matthews A;Renaud JB;Caillet M;Marsh M;Berlioz-Torrent C
通讯作者：
Berlioz-Torrent C
影响因子：
5.7
作者：
Agromayor, Monica;Soler, Nicolas;Caballe, Anna;Kueck, Tonya;Freund, Stefan M.;Allen, Mark D.;Bycroft, Mark;Perisic, Olga;Ye, Yu;McDonald, Bethan;Scheel, Hartmut;Hofmann, Kay;Neil, Stuart J. D.;Martin-Serrano, Juan;Williams, Roger L.
通讯作者：
Williams, Roger L.
影响因子：
64.8
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
通讯作者：
Luban, Jeremy
影响因子：
6.7
作者：
McNatt, Matthew W.;Zang, Trinity;Hatziioannou, Theodora;Bartlett, Mackenzie;Ben Fofana, Ismael;Johnson, Welkin E.;Neil, Stuart J. D.;Bieniasz, Paul D.
通讯作者：
Bieniasz, Paul D.