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ATM supports gammaherpesvirus replication by attenuating type I interferon pathway. Virology 2017 10;510:137-146

Date

07/22/2017

Pubmed ID

28732227

Pubmed Central ID

PMC5570481

DOI

10.1016/j.virol.2017.07.014

Scopus ID

2-s2.0-85024386889   3 Citations

Abstract

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 VL

Author

Vera Tarakanova PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Ataxia Telangiectasia Mutated Proteins
Cells, Cultured
Host-Pathogen Interactions
Interferon Type I
Macrophages
Mice, Inbred C57BL
Mice, Knockout
Rhadinovirus
Virus Replication
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a