title: Mouse gammaherpesvirus-68 infection acts as a rheostat to set the level of type I interferon signaling in primary macrophages.
abstract: Type I interferon (IFN) is a critical antiviral response of the host. We found that Interferon Regulatory Factor 3 (IRF-3) was responsible for induction of type I IFN following mouse gammaherpesvirus-68 (MHV68) infection of primary macrophages. Intriguingly, type I IFN signaling was maintained throughout the entire MHV68 replication cycle, in spite of several known viral IFN antagonists. However, MHV68-infected primary macrophages displayed attenuated responses to exogenous type I IFN, suggesting that MHV68 controls the level of type I IFN signaling that is allowed to occur during replication. Type I IFN receptor and IRF-3 were necessary to attenuate transcription of MHV68 RTA, an immediate early gene critical for replication. Furthermore, higher constitutive activity of RTA promoters was observed in the absence of type I IFN signaling. Our study suggests that MHV68 has preserved the ability to sense type I IFN status of the host in order to limit lytic replication.
authors.affiliation: Department of Microbiology and Molecular Genetics, Cancer Center, Medical College of Wisconsin, USA.
authors.forename: Brittani M
authors.initials: BM
authors.lastname: Wood
authors.forename: Wadzanai P
authors.initials: WP
authors.lastname: Mboko
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Mounce
authors.forename: Vera L
authors.initials: VL
authors.lastname: Tarakanova
mesh_terms: D000818:Animals; D017874:Immediate-Early Proteins / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D051379:Mice; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D018144:Rhadinovirus / Q000276:immunology* / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta