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Journal of Virology, May 2003, p. 5118-5126, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5118-5126.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Maintenance of Gammaherpesvirus Latency Requires Viral Cyclin in the Absence of B Lymphocytes

Linda F. van Dyk,1* Herbert W. Virgin IV,2 and Samuel H. Speck3

Department of Microbiology and Immunology, University of Colorado Health Science Center, Denver, Colorado 80262,1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110,2 Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 303293

Received 17 December 2002/ Accepted 4 February 2003

Gammaherpesviruses establish a life-long chronic infection that is tightly controlled by the host immune response. We previously demonstrated that viruses lacking the gammaherpesvirus 68 ({gamma}HV68) viral cyclin (v-cyclin) exhibited a severe defect in reactivation from latency and persistent replication. In this analysis of chronic infection, we demonstrate that the v-cyclin is required for {gamma}HV68-associated mortality in B-cell-deficient mice. Furthermore, we identify the v-cyclin as the first gene product required for maintenance of gammaherpesvirus latency in vivo in the absence of B lymphocytes. While the v-cyclin was necessary for maintenance of latency in the absence of B cells, maintenance of v-cyclin-deficient viruses was equivalent to that of wild-type {gamma}HV68 in the presence of B cells. These results support a model in which maintenance of chronic {gamma}HV68 infection requires v-cyclin-dependent reactivation and reseeding of non-B-cell latency reservoirs in the absence of B cells and raise the possibility that B cells represent a long-lived latency reservoir maintained independently of reactivation. These results highlight distinct mechanisms for the maintenance of chronic infection in immunocompetent and B-cell-deficient mice and suggest that the different latency reservoirs have distinct gene requirements for the maintenance of latency.

* Corresponding author. Mailing address: Department of Microbiology, Box B-175, University of Colorado Health Science Center, 4200 E. Ninth Ave., Denver, CO 80262. Phone: (303) 315-8991. Fax: (303) 315-6785. E-mail: linda.vandyk{at}uchsc.edu.

Journal of Virology, May 2003, p. 5118-5126, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5118-5126.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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