Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Nat Immunol. 2017 Feb;18(2):225-235. doi: 10.1038/ni.3647. Epub 2016 Dec 26.
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS. Notably, HIV-1 recognition by the C-type lectin receptor DC-SIGN activated the mitotic kinase PLK1, which suppressed signaling downstream of MAVS, thereby interfering with intrinsic host defense during HIV-1 infection. Finally, we showed that PLK1-mediated suppression of DDX3-MAVS signaling was a viral strategy that accelerated HIV-1 replication in infected individuals.
人类免疫缺陷病毒 1（HIV-1）逃避树突状细胞（DC）免疫监视并因此阻止保护性适应性免疫反应的机制仍知之甚少。在这里，我们表明 HIV-1 通过 DC 主动阻止抗病毒免疫反应，这有助于感染个体中 HIV-1 的有效复制。我们鉴定出 RNA 解旋酶 DDX3 作为 HIV-1 的传感器，该传感器在 HIV-1 感染后结合无功能的 HIV-1 RNA，并通过信号衔接子 MAVS 诱导 DC 成熟和 I 型干扰素反应。值得注意的是，C 型凝集素受体 DC-SIGN 对 HIV-1 的识别激活了有丝分裂激酶 PLK1，其抑制了 MAVS 下游的信号，从而在 HIV-1 感染期间干扰了固有宿主防御。最后，我们表明，PLK1 介导的 DDX3-MAVS 信号抑制是一种病毒策略，可加速感染个体中 HIV-1 的复制。
