In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity. However, the antiviral functions of helicase SF1, which shares a conserved helicase core with SF2, are little understood. Here we demonstrate that zinc finger NFX1-type containing 1 (ZNFX1), a helicase SF1, is an interferon (IFN)-stimulated, mitochondrial-localised dsRNA sensor that specifically restricts the replication of RNA viruses. Upon virus infection, ZNFX1 immediately recognizes viral RNA through its Armadillo-type fold and P-loop domain and then interacts with mitochondrial antiviral signalling protein to initiate the type I IFN response without depending on retinoic acid-inducible gene I-like receptors (RLRs). In short, as is the case with interferon-stimulated genes (ISGs) alone, ZNFX1 can induce IFN and ISG expression at an early stage of RNA virus infection to form a positively regulated loop of the well-known RLR signalling. This provides another layer of understanding of the complexity of antiviral immunity.

中文翻译：

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线粒体定位的 ZNFX1 作为 dsRNA 传感器通过 MAVS 启动抗病毒反应。

在过去的二十年中，新兴研究表明，属于解旋酶超家族 2 (SF2) 的 DExD/H 盒解旋酶在抗病毒先天免疫中发挥着重要作用。然而，与 SF2 共享一个保守的解旋酶核心的解旋酶 SF1 的抗病毒功能却鲜为人知。在这里，我们证明了含有 1 (ZNFX1) 的锌指 NFX1 型，一种解旋酶 SF1，是一种干扰素 (IFN) 刺激的线粒体定位 dsRNA 传感器，专门限制 RNA 病毒的复制。病毒感染后，ZNFX1 立即通过其犰狳型折叠和 P 环结构域识别病毒 RNA，然后与线粒体抗病毒信号蛋白相互作用以启动 I 型 IFN 反应，而不依赖于维甲酸诱导基因 I 样受体 (RLR) . 简而言之，与单独使用干扰素刺激基因 (ISG) 的情况一样，ZNFX1 可以在 RNA 病毒感染的早期诱导 IFN 和 ISG 表达，从而形成众所周知的 RLR 信号传导的正调控环。这提供了对抗病毒免疫复杂性的另一层理解。