The Journal of Experimental Medicine
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Published 18 November 2002. doi:10.1084/jem.20020890
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© Rockefeller University Press, 0022-1007/2002/11/1363/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 10, November 18, 2002 1363-1372

{gamma}-Herpesvirus Latency Is Preferentially Maintained in Splenic Germinal Center and Memory B Cells

Emilio Flaño, In-Jeong Kim, David L. Woodland and Marcia A. Blackman

Trudeau Institute, Saranac Lake, NY 12983

Address correspondence to Marcia A. Blackman, Trudeau Institute, 100 Algonquin Avenue, Saranac Lake, NY 12983. Phone: 518-891-3080; Fax: 518-891-5126; E-mail: mblackman{at}trudeauinstitute.org

The {gamma}-herpesviruses are oncogenic B cell lymphotrophic viruses that establish life-long latency in the host. Murine {gamma}-herpesvirus 68 (MHV-68) infection of mice represents a unique system for analyzing {gamma}-herpesvirus latency in splenic B cells at different stages of infection. After intranasal infection with MHV-68 we analyzed the establishment of latency 14 days after infection, and the maintenance of latency 3 months after infection in different purified subpopulations of B cells in the spleen. The data show that MHV-68 latency is mainly established in germinal center B cells and that long-term latency is preferentially maintained in two different subsets of isotype-switched B cells, germinal center and memory B cells. Cell cycle analysis indicates that MHV-68 is located in both cycling and resting isotype-switched B cells. Analysis of viral gene expression showed that both lytic and latent viral transcripts were differentially expressed in germinal center and memory B cells during long-term latency. Together, these observations suggested that {gamma}-herpesviruses exploit the B cell life cycle in the spleen.

Key Words: murine herpesvirus 68 • gammaherpesvirinae • viral latency • B lymphocytes • germinal centers


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