期刊
JOURNAL OF VIROLOGY
卷 86, 期 23, 页码 12826-12837出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00917-12
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资金
- Concern Foundation, an American Cancer Society Research Scholar Award, Advancing Healthier Wisconsin [RSG-12-174-01-MPC]
- American Cancer Society Research Scholar Award [RSG-12-174-01-MPC]
- Medical College of Wisconsin Cancer Center
- Medical College of Wisconsin, Children's Research Institute
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.
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