Unraveling immunity to gamma-herpesviruses: a new model for understanding the role of immunity in chronic virus infection.
Murine gamma-herpesvirus 68 (gammaHV68) infection is a new model for understanding how immunity and chronic gamma-herpesvirus infection inter-relate. gammaHV68 is closely related to the human Epstein-Barr virus and Kaposi's sarcoma herpesvirus and is associated with tumors, vasculitis of the great elastic arteries and splenic fibrosis. Advances in the past year have provided an even stronger foundation for believing that gammaHV68 infection of normal and mutant mice will become the pre-eminent animal model for understanding gamma-herpesvirus pathogenesis and immunity. gammaHV68 latency has been characterized employing new assays for quantitating cells carrying the gammaHV68 genome and cells that reactivate gammaHV68 and for detecting the presence of preformed infectious virus in tissues. These advances have fostered the first steps towards a molecular definition of gammaHV68 latency. It appears that gammaHV68 shares latency programs with human gamma-herpesviruses - including the loci for gene 73, v-bcl-2 and the viral homolog of the G-protein coupled receptor. This provides candidate antigens for analysis of the role of T and B cells in regulating latency. Multiple cellular reservoirs for gammaHV68 latency were uncovered with the demonstration that gammaHV68 latently infects macrophages in addition to B cells. A critical role for B cells in regulating the nature of gammaHV68 latency was discovered and the mechanism was shown to be via alteration of the efficiency of reactivation. Studies of the response of CD4(+) and CD8(+) cells during acute and chronic gammaHV68 were performed. These new studies provide key building blocks for further development of this novel and interesting model system.
Virgin
H W
HW
Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA. virgin@immunology.wustl.edu
Speck
S H
SH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002908:Chronic Disease; D018142:Gammaherpesvirinae / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D017735:Virus Latency
D007371:Interferon-gamma