HTLV-1 Tax impairs K63-linked ubiquitination of STING to evade host innate immunity.
HTLV-1 Tax impairs K63-linked ubiquitination of STING to evade host innate immunity.
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HTLV-1 Tax 会损害 STING 的 K63 泛素化，从而逃避宿主先天免疫。
DOI：
10.1016/j.virusres.2017.01.016
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发表时间：
2017-03-15
期刊：
影响因子：
5
通讯作者：
Yang, Bo
中科院分区：
文献类型：
--
作者：
Wang, Jie;Yang, Shuai;Yang, Bo
细胞抗病毒的先天免疫系统对于宿主的防御是必不可少的，病毒已经进化出各种策略来逃避先天免疫。人嗜T淋巴细胞病毒1型(HTLV-1)属于三角洲逆转录病毒家族，可在人类体内持续感染多年。然而，这种病毒如何逃避宿主的先天免疫反应仍不清楚。在这里，我们报告了HTLV-1用来阻断先天性免疫反应的一种新策略。我们观察到干扰素基因刺激物(STINT)限制HTLV-1蛋白的表达，并且在PMA-THP1(PMA-THP1)细胞中HTLV-1逆转录中间体(RTI)s5DNA90触发的干扰素(IFN)-β的产生起关键作用。HTLV-1蛋白TAX可抑制STING诱导的干扰素-β转录激活。Tax还抑制聚(da：dt)、干扰素刺激性DNA(ISD)或环状GMP-AMP(CGAMP)刺激的干扰素-β的产生，这依赖于刺激物的激活。免疫共沉淀分析和共聚焦显微镜表明，在同一复合体中，紫杉醇与刺痛有关。机制研究表明，TAX减少了K63连接的STING的泛素化，并破坏了STING和坦克结合蛋白1(TBKI)之间的相互作用。这些发现可能会进一步揭示HTLV-1感染的分子机制。(C)2017爱思唯尔B.V.保留所有权利。
The cellular antiviral innate immune system is essential for host defense and viruses have evolved a variety of strategies to evade the innate immunity. Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and it can establish persistent infection in human beings for many years. However, how this virus evades the host innate immune responses remains unclear. Here we report a new strategy used by HTLV-1 to block innate immune responses. We observed that stimulator of interferon genes (STING) limited HTLV-1 protein expression and was critical to HTLV-1 reverse transcription intermediate (RTI) s5DNA90 triggered interferon (IFN)-beta production in phorbo112-myristate13-acetate (PMA)-differentiated THP1 (PMA-THP1) cells. The HTLV-1 protein Tax inhibited STING overexpression induced transcriptional activation of IFN-beta. Tax also impaired poly(dA:dT), interferon stimulatory DNA (ISD) or cyclic GMP-AMP (cGAMP) stimulated IFN-beta production, which was dependent on STING activation. Coimmunoprecipitation assays and confocal microscopy indicated that Tax was associated with STING in the same complex. Mechanistic studies suggested that Tax decreased the K63-linked ubiquitination of STING and disrupted the interactions between STING and TANK-binding kinase 1 (TBKI). These findings may shed more light on the molecular mechanisms underlying HTLV-1 infection. (C) 2017 Elsevier B.V. All rights reserved.