title: Inhibition of IFN-gamma signaling by an Epstein-Barr virus immediate-early protein.
abstract: Viruses have evolved elaborate mechanisms to target many aspects of the host's immune response. The cytokine IFN-gamma plays a central role in resistance of the host to infection via direct antiviral effects as well as modulation of the immune response. In this study, we demonstrate that the Epstein-Barr virus (EBV) immediate-early protein, BZLF1, inhibits the IFN-gamma signaling pathway. BZLF1 decreases the ability of IFN-gamma to activate a variety of important downstream target genes, such as IRF-1, p48, and CIITA, and prevents IFN-gamma-induced class II MHC surface expression. Additionally, BZLF1 inhibits IFN-gamma-induced STAT1 tyrosine phosphorylation and nuclear translocation. Finally, we demonstrate that BZLF1 decreases expression of the IFN-gamma receptor, suggesting a mechanism by which EBV may escape antiviral immune responses during primary infection.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Morrison
authors.forename: A
authors.initials: A
authors.lastname: Mauser
authors.forename: A
authors.initials: A
authors.lastname: Wong
authors.forename: J P
authors.initials: JP
authors.lastname: Ting
authors.forename: S C
authors.initials: SC
authors.lastname: Kenney
mesh_terms: D004268:DNA-Binding Proteins / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology*; D014764:Viral Proteins
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D007371:Interferon-gamma