甲型流感病毒 NS1 通过诱导溶血磷脂酸酶降解来阻碍宿主固有免疫反应。
Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response.
机构信息
Department of Surgery, University of Missouri, Columbia, MO, 65212, USA; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, 65212, USA.
Department of Surgery, University of Missouri, Columbia, MO, 65212, USA; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, 65212, USA; Present Address: State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.
出版信息
Virology. 2021 Jun;558:67-75. doi: 10.1016/j.virol.2021.02.006. Epub 2021 Mar 13.
The type I interferon (IFN)-mediated innate immune response is one of the central obstacles influenza A virus (IAV) must overcome in order to successfully replicate within the host. We have previously shown that sphingosine 1-phosphate (S1P) lyase (SPL) enhances IKKϵ-mediated type I IFN responses. Here, we demonstrate that the nonstructural protein 1 (NS1) of IAV counteracts the SPL-mediated antiviral response by inducing degradation of SPL. SPL was ubiquitinated and downregulated upon IAV infection or NS1 expression, whereas NS1-deficient IAV failed to elicit SPL ubiquitination or downregulation. Transiently overexpressed SPL increased phosphorylation of IKKϵ, resulting in enhanced expression of type I IFNs. However, this induction was markedly inhibited by IAV NS1. Collectively, this study reveals a novel strategy employed by IAV to subvert the type I IFN response, providing new insights into the interplay between IAV and host innate immunity.
I 型干扰素（IFN）介导的先天免疫反应是甲型流感病毒（IAV）在宿主中成功复制所必须克服的核心障碍之一。我们之前已经表明，鞘氨醇 1-磷酸（S1P）裂解酶（SPL）增强 IKKϵ 介导的 I 型 IFN 反应。在这里，我们证明 IAV 的非结构蛋白 1（NS1）通过诱导 SPL 降解来对抗 SPL 介导的抗病毒反应。SPL 在 IAV 感染或 NS1 表达时被泛素化和下调，而缺乏 NS1 的 IAV 则不能引发 SPL 泛素化或下调。瞬时过表达 SPL 增加了 IKKϵ 的磷酸化，导致 I 型 IFN 的表达增强。然而，这种诱导被 IAV NS1 明显抑制。总之，这项研究揭示了 IAV 用来颠覆 I 型 IFN 反应的一种新策略，为 IAV 与宿主先天免疫之间的相互作用提供了新的见解。
Zotero 插件