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Ataxia telangiectasia mutated kinase controls chronic gammaherpesvirus infection. J Virol 2012 Dec;86(23):12826-37

Date

09/21/2012

Pubmed ID

22993144

Pubmed Central ID

PMC3497635

DOI

10.1128/JVI.00917-12

Scopus ID

2-s2.0-84869205619   24 Citations

Abstract

Gammaherpesviruses, such as Epstein-Barr virus (EBV), are ubiquitous cancer-associated pathogens that interact with DNA damage response, a tumor suppressor network. Chronic gammaherpesvirus infection and pathogenesis in a DNA damage response-insufficient host are poorly understood. Ataxia-telangiectasia (A-T) is associated with insufficiency of ataxia-telangiectasia mutated (ATM), a critical DNA damage response kinase. A-T patients display a pattern of anti-EBV antibodies suggestive of poorly controlled EBV replication; however, parameters of chronic EBV infection and pathogenesis in the A-T population remain unclear. Here we demonstrate that chronic gammaherpesvirus infection is poorly controlled in an animal model of A-T. Intriguingly, in spite of a global increase in T cell activation and numbers in wild-type (wt) and ATM-deficient mice in response to mouse gammaherpesvirus 68 (MHV68) infection, the generation of an MHV68-specific immune response was altered in the absence of ATM. Our finding that ATM expression is necessary for an optimal adaptive immune response against gammaherpesvirus unveils an important connection between DNA damage response and immune control of chronic gammaherpesvirus infection, a connection that is likely to impact viral pathogenesis in an ATM-insufficient host.

Author List

Kulinski JM, Leonardo SM, Mounce BC, Malherbe L, Gauld SB, 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
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins
Cell Line
DNA Damage
DNA-Binding Proteins
Flow Cytometry
Gammaherpesvirinae
Herpesviridae Infections
Lymphocyte Activation
Mice
Polymerase Chain Reaction
Protein-Serine-Threonine Kinases
T-Lymphocytes
Tumor Suppressor Proteins
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a