Title Guanylate Binding Protein 4 Negatively Regulates Virus-Induced Type I IFN and Antiviral Response by Targeting IFN Regulatory Factor 7
Authors Hu, Yu
Wang, Jie
Yang, Bo
Zheng, Nuoyan
Qin, Meiling
Ji, Yongyong
Lin, Guomei
Tian, Lin
Wu, Xiaodong
Wu, Li
Sun, Bing
Affiliation Chinese Acad Sci, Lab Mol Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
Peking Univ, Tsinghua Univ, Joint Ctr Life Sci, Beijing 100084, Peoples R China.
Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
Chinese Acad Sci, Mol Virus Unit, Key Lab Mol Virol & Immunol, Inst Pasteur Shanghai, Shanghai 200025, Peoples R China.
Chinese Acad Sci, Lab Mol Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Rd, Shanghai 200031, Peoples R China.
Keywords TOLL-LIKE RECEPTOR
NF-KAPPA-B
INTERFERON-ALPHA INDUCTION
INNATE IMMUNITY
RIG-I
MEDIATED DEGRADATION
PATHOGEN RECOGNITION
INDUCIBLE GTPASES
DENDRITIC CELLS
RNA HELICASE
Issue Date 2011
Publisher journal of immunology
Citation JOURNAL OF IMMUNOLOGY.2011,187,(12),6456-6462.
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-kappa B 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. The Journal of Immunology, 2011, 187: 6456-6462.
URI http://hdl.handle.net/20.500.11897/394039
ISSN 0022-1767
DOI 10.4049/jimmunol.1003691
Indexed SCI(E)
Appears in Collections: 生命科学学院

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