ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection. Virology 2015 Sep;483:264-74
Date
05/24/2015Pubmed ID
26001649Pubmed Central ID
PMC4516584DOI
10.1016/j.virol.2015.04.026Scopus ID
2-s2.0-84929458199 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo.
Author List
Kulinski JM, Darrah EJ, Broniowska KA, Mboko WP, Mounce BC, Malherbe LP, Corbett JA, Gauld SB, Tarakanova VLAuthors
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinVera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAnimals
Ataxia Telangiectasia Mutated Proteins
Chronic Disease
Gammaherpesvirinae
Herpesviridae Infections
Host-Pathogen Interactions
Humans
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells
Virus Activation