HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4+ T Cells.
HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4+ T Cells.
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DOI：
10.1016/j.celrep.2016.09.023
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发表时间：
2016-10
期刊：
影响因子：
8.8
通讯作者：
J. Vermeíre;F. Roesch;D. Sauter;Rejane Rua;Dominik Hotter;A. V. Van Nuffel;H. Vanderstraeten;E. Naessens;Veronica Iannucci;Alessia Landi;Wojciech Witkowski;Ann Baeyens;F. Kirchhoff;B. Verhasselt
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文献类型：
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作者：
J. Vermeíre;F. Roesch;D. Sauter;Rejane Rua;Dominik Hotter;A. V. Van Nuffel;H. Vanderstraeten;E. Naessens;Veronica Iannucci;Alessia Landi;Wojciech Witkowski;Ann Baeyens;F. Kirchhoff;B. Verhasselt
几种模式识别受体感知HIV-1复制产物，并在特定实验条件下诱导I型干扰素（IFN-I）产生。然而，据认为，病毒感应和IFN诱导在体内HIV-1的主要靶细胞中几乎不存在。在这里，我们表明活化的CD 4 +T细胞通过胞质DNA传感器cGAS感知HIV-1感染，并产生生物活性的IFN-I应答。通过HIV-1感染有效诱导IFN-I需要前病毒整合，并受新表达的病毒辅助蛋白的调节：Vpr增强，而Vpu抑制cGAS依赖性IFN-I诱导。此外，Vpr还增强了Vpx处理的树突状细胞中HIV-1感染的先天感应。我们的研究结果确定cGAS作为CD 4 +T细胞中对HIV-1感染的IFN-I应答的介体，并证明该应答由病毒辅助蛋白Vpr和Vpu调节。因此，在HIV-1的主要靶细胞中，病毒先天免疫逃避是不完整的。
Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated dendritic cells. Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4+T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1.