ATM supports gammaherpesvirus replication by attenuating type I interferon pathway. Virology 2017 Oct;510:137-146
Date
07/22/2017Pubmed ID
28732227Pubmed Central ID
PMC5570481DOI
10.1016/j.virol.2017.07.014Scopus ID
2-s2.0-85024386889 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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.
Author List
Darrah EJ, Stoltz KP, Ledwith M, Tarakanova VLAuthor
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAtaxia Telangiectasia Mutated Proteins
Cells, Cultured
Host-Pathogen Interactions
Interferon Type I
Macrophages
Mice, Inbred C57BL
Mice, Knockout
Rhadinovirus
Virus Replication
