TY - JOUR
T1 - Unraveling immunity to γ-herpesviruses
T2 - A new model for understanding the role of immunity in chronic virus infection
AU - Virgin IV, Herbert W.
AU - Speck, Samuel H.
N1 - Funding Information:
HWV was supported by National Institutes for Health ROl grant AI39616 from the National Institure of Allergy and Infectious Diseases, grant RPG-97-134-Ol-MBC from the American Cancer Society and by the Monsanto-Sea& Biomedical Agreement. HWV and SHS were supported by National Institures for Health ROl grants HL60090 from the National Heart, Lung and Blood Institute, and CA74730 from the National Cancer Institute. SHS was supported by National Instirutes for Health ROl grants CA43143, CA52004 and CA58524 from the National Cancer Institute and by the Monsanto-Searle Biomedical Agreement. We would like to acknowledge helpful discussions from members of the Speck and Virgin laboratories during the course of this work, as well as discussions thar occurred during laboratory meetings shared with David Leib. We appreciate the comments of Linda Van Dyk, Albert Dal Canto, Rachel Presti, Sharookh Kapadia, Stuart Resnick, Iglika Pavlova and Victor van Berkel on the manuscript.
PY - 1999/8
Y1 - 1999/8
N2 - Murine γ-herpesvirus 68 (γHV68) infection is a new model for understanding how immunity and chronic γ-herpesvirus infection inter-relate. γHV68 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 γHV68 infection of normal and mutant mice will become the pre-eminent animal model for understanding γ-herpesvirus pathogenesis and immunity. γHV68 latency has been characterized employing new assays for quantitating cells carrying the γHV68 genome and cells that reactivate γHV68 and for detecting the presence of preformed infectious virus in tissues. These advances have fostered the first steps towards a molecular definition of γHV68 latency. It appears that γHV68 shares latency programs with human γ-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 γHV68 latency were uncovered with the demonstration that γHV68 latently infects macrophages in addition to B cells. A critical role for B cells in regulating the nature of γHV68 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 γHV68 were performed. These new studies provide key building blocks for further development of this novel and interesting model system.
AB - Murine γ-herpesvirus 68 (γHV68) infection is a new model for understanding how immunity and chronic γ-herpesvirus infection inter-relate. γHV68 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 γHV68 infection of normal and mutant mice will become the pre-eminent animal model for understanding γ-herpesvirus pathogenesis and immunity. γHV68 latency has been characterized employing new assays for quantitating cells carrying the γHV68 genome and cells that reactivate γHV68 and for detecting the presence of preformed infectious virus in tissues. These advances have fostered the first steps towards a molecular definition of γHV68 latency. It appears that γHV68 shares latency programs with human γ-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 γHV68 latency were uncovered with the demonstration that γHV68 latently infects macrophages in addition to B cells. A critical role for B cells in regulating the nature of γHV68 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 γHV68 were performed. These new studies provide key building blocks for further development of this novel and interesting model system.
UR - http://www.scopus.com/inward/record.url?scp=0033178351&partnerID=8YFLogxK
U2 - 10.1016/S0952-7915(99)80063-6
DO - 10.1016/S0952-7915(99)80063-6
M3 - Article
C2 - 10448140
AN - SCOPUS:0033178351
SN - 0952-7915
VL - 11
SP - 371
EP - 379
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
IS - 4
ER -