Mouse gammaherpesvirus-68 infection acts as a rheostat to set the level of type I interferon signaling in primary macrophages

作者：Wood Brittani M; Mboko Wadzanai P; Mounce Bryan C; Tarakanova Vera L^*

来源：Virology, 2013, 443(1): 123-133.

DOI：10.1016/j.virol.2013.04.036

• Type I interferon
• Gammaherpesvirus
• Interferon regulatory factor 3
• RTA
• Macrophage

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.

• 出版日期2013-8-15