title: Regulation of antiviral innate immunity by deubiquitinase CYLD.
abstract: 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.
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Minying
authors.initials: M
authors.lastname: Zhang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lee
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000074749:Deubiquitinating Enzyme CYLD; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D015996:Survival Rate; D054243:Vesicular Stomatitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D016899:Interferon-beta; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD; D003546:Cysteine Endopeptidases