title: Guanylate binding protein 4 negatively regulates virus-induced type I IFN and antiviral response by targeting IFN regulatory factor 7.
abstract: IRF7 is known as the master regulator in virus-triggered induction of type I IFNs (IFN-I). In this study, we identify GBP4 virus-induced protein interacting with IRF7 as a negative regulator for IFN-I response. Overexpression of GBP4 inhibits virus-triggered activation of IRF7-dependent signaling, but has no effect on NF-κB signaling, whereas the knockdown of GBP4 has opposite effects. Furthermore, the supernatant from Sendai virus-infected cells in which GBP4 have been silenced inhibits the replication of vesicular stomatitis virus more efficiently. Competitive coimmunoprecipitation experiments indicate that overexpression of GBP4 disrupts the interactions between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination. Our results suggest that GBP4 is a negative regulator of virus-triggered IFN-I production, and it is identified as a novel protein targeting IRF7 and inhibiting its function.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Nuoyan
authors.initials: N
authors.lastname: Zheng
authors.forename: Meiling
authors.initials: M
authors.lastname: Qin
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Ji
authors.forename: Guomei
authors.initials: G
authors.lastname: Lin
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D057809:HEK293 Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051379:Mice; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D029082:Sendai virus / Q000276:immunology*; D048029:TNF Receptor-Associated Factor 6 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D011994:Recombinant Proteins; D048029:TNF Receptor-Associated Factor 6; D019204:GTP-Binding Proteins; C472530:Mpa2 protein, mouse