title: ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection.
abstract: 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.
authors.affiliation: Microbiology and Molecular Genetics, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Kulinski
authors.affiliation: Microbiology and Molecular Genetics, United States.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Darrah
authors.affiliation: Biochemistry, Medical College of Wisconsin, United States.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Broniowska
authors.affiliation: Microbiology and Molecular Genetics, United States.
authors.forename: Wadzanai P
authors.initials: WP
authors.lastname: Mboko
authors.affiliation: Microbiology and Molecular Genetics, United States.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Mounce
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, United States.
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Malherbe
authors.affiliation: Biochemistry, Medical College of Wisconsin, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Corbett
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Pediatrics, United States.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gauld
authors.affiliation: Microbiology and Molecular Genetics, United States; Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States. Electronic address: vera@mcw.edu.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Tarakanova
mesh_terms: D000328:Adult; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000172:deficiency / Q000378:metabolism; D002908:Chronic Disease; D018142:Gammaherpesvirinae / Q000502:physiology*; D006566:Herpesviridae Infections / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000821:virology*; D014775:Virus Activation
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse
keywords: ATM; Gammaherpesvirus; Myeloid cell; Reactivation; T cell response