DDX1、DDX21 和 DHX36 解旋酶与衔接分子 TRIF 形成复合物，以在树突状细胞中感知 dsRNA。
DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells.
机构信息
Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Immunity. 2011 Jun 24;34(6):866-78. doi: 10.1016/j.immuni.2011.03.027.
Abstract
The innate immune system detects viral infection predominantly by sensing viral nucleic acids. We report the identification of a viral sensor, consisting of RNA helicases DDX1, DDX21, and DHX36, and the adaptor molecule TRIF, by isolation and sequencing of poly I:C-binding proteins in myeloid dendritic cells (mDCs). Knockdown of each helicase or TRIF by shRNA blocked the ability of mDCs to mount type I interferon (IFN) and cytokine responses to poly I:C, influenza A virus, and reovirus. Although DDX1 bound poly I:C via its Helicase A domain, DHX36 and DDX21 bound the TIR domain of TRIF via their HA2-DUF and PRK domains, respectively. This sensor was localized within the cytosol, independent of the endosomes. Thus, the DDX1-DDX21-DHX36 complex represents a dsRNA sensor that uses the TRIF pathway to activate type I IFN responses in the cytosol of mDCs.
摘要
先天免疫系统主要通过检测病毒核酸来检测病毒感染。我们通过分离和测序髓样树突状细胞（mDCs）中多聚 I：C 结合蛋白，鉴定了一个由 RNA 解旋酶 DDX1、DDX21 和 DHX36 以及衔接分子 TRIF 组成的病毒传感器。通过 shRNA 敲低每种解旋酶或 TRIF 均可阻断 mDC 对多聚 I：C、甲型流感病毒和呼肠孤病毒产生 I 型干扰素（IFN）和细胞因子反应的能力。尽管 DDX1 通过其 Helicase A 结构域与多聚 I：C 结合，但 DHX36 和 DDX21 分别通过其 HA2-DUF 和 PRK 结构域与 TRIF 的 TIR 结构域结合。该传感器位于细胞质中，不依赖于内体。因此，DDX1-DDX21-DHX36 复合物代表一种 dsRNA 传感器，它利用 TRIF 途径在 mDCs 的细胞质中激活 I 型 IFN 反应。
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2
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3
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6
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7
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