ATM supports gammaherpesvirus replication by attenuating type I interferon pathway

作者：Darrah Eric J; Stoltz Kyle P; Ledwith Mitchell; Tarakanova Vera L^*

来源：Virology, 2017, 510: 137-146.

DOI：10.1016/j.virol.2017.07.014

• Gammaherpesvirus
• Type I interferon
• ATM
• Viral replication

Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection.

• 出版日期2017-10