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Journal of Virology, January 2006, p. 192-200, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.192-200.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency

Ashley L. Steed,1 Erik S. Barton,1 Scott A. Tibbetts,1 Daniel L. Popkin,1 Mary L. Lutzke,2 Rosemary Rochford,2 and Herbert W. Virgin IV1*

Department of Pathology and Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110,1 Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York 132102

Received 29 June 2005/ Accepted 16 September 2005

Establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. Interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. Prior studies show that mice deficient in gamma interferon (IFN-{gamma}) or the IFN-{gamma} receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 ({gamma}HV68) latency, produce infectious virus after the establishment of latency, and develop large-vessel vasculitis. Here, we demonstrate that IFN-{gamma} is a powerful inhibitor of reactivation of {gamma}HV68 from latency in tissue culture. In vivo, IFN-{gamma} controls viral gene expression during latency. Importantly, depletion of IFN-{gamma} in latently infected mice results in an increased frequency of cells reactivating virus. This demonstrates that IFN-{gamma} is important for immune surveillance that limits reactivation of {gamma}HV68 from latency.

* Corresponding author. Mailing address: Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-9223. Fax: (314) 362-4096. E-mail: virgin{at}wustl.edu.

Journal of Virology, January 2006, p. 192-200, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.192-200.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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