Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cell Mol Immunol. 2011 Nov;8(6):502-4. doi: 10.1038/cmi.2011.42. Epub 2011 Sep 26.
An antiviral innate immune response involves induction of type I interferons (IFNs) and their subsequent autocrine and paracrine actions, but the underlying regulatory mechanisms are incompletely understood. Here we report that CYLD, a deubiquitinase that specifically digests lysine 63-linked ubiquitin chains, is required for antiviral host defense. Loss of CYLD renders mice considerably more susceptible to infection by vesicular stomatitis virus (VSV). Consistently, CYLD-deficient dendritic cells are more sensitive to VSV infection. This functional defect was not due to lack of type I IFN production but rather because of attenuated IFN receptor signaling. In the absence of CYLD, IFN-β is ineffective in the induction of antiviral genes and protection of cells from viral infection. These findings establish CYLD as a novel regulator of antiviral innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.
抗病毒先天免疫反应涉及诱导 I 型干扰素 (IFN) 及其随后的自分泌和旁分泌作用，但潜在的调节机制尚不完全清楚。在这里，我们报告称，去泛素化酶 CYLD 是一种特异性消化赖氨酸 63 连接的泛素链的酶，是抗病毒宿主防御所必需的。CYLD 的缺失使小鼠更容易感染水疱性口炎病毒 (VSV)。一致地，CYLD 缺陷型树突状细胞对 VSV 感染更为敏感。这种功能缺陷不是由于缺乏 I 型 IFN 产生，而是由于 IFN 受体信号转导减弱。在没有 CYLD 的情况下，IFN-β 无法有效诱导抗病毒基因并保护细胞免受病毒感染。这些发现确立了 CYLD 作为抗病毒先天免疫的新型调节剂，并表明 CYLD 在调节 IFN 受体信号转导中的作用。
