title: Gamma interferon blocks gammaherpesvirus reactivation from latency.
abstract: 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.
authors.affiliation: Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Steed
authors.forename: Erik S
authors.initials: ES
authors.lastname: Barton
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tibbetts
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Popkin
authors.forename: Mary L
authors.initials: ML
authors.lastname: Lutzke
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rochford
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: 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
chemical_list: D017471:Receptors, Interferon; D007371:Interferon-gamma