Gamma interferon blocks gammaherpesvirus reactivation from latency.
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 (gammaHV68) 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 gammaHV68 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 gammaHV68 from latency.
Steed
Ashley L
AL
Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Ave., St. Louis, MO 63110, USA.
Barton
Erik S
ES
Tibbetts
Scott A
SA
Popkin
Daniel L
DL
Lutzke
Mary L
ML
Rochford
Rosemary
R
Virgin
Herbert W
HW
D000818:Animals; D018142:Gammaherpesvirinae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006566:Herpesviridae Infections / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D017735:Virus Latency / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D017471:Receptors, Interferon; D007371:Interferon-gamma