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Guanylate binding protein 4 negatively regulates virus-induced type I IFN and antiviral response by targeting IFN regulatory factor 7.

Authors :
Hu Y
Wang J
Yang B
Zheng N
Qin M
Ji Y
Lin G
Tian L
Wu X
Wu L
Sun B
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Dec 15; Vol. 187 (12), pp. 6456-62. Date of Electronic Publication: 2011 Nov 16.
Publication Year :
2011

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.

Details

Language :
English
ISSN :
1550-6606
Volume :
187
Issue :
12
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
22095711
Full Text :
https://doi.org/10.4049/jimmunol.1003691