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Journal of Virology, June 1999, p. 4651-4661, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

B Cells Regulate Murine Gammaherpesvirus 68 Latency

Karen E. Weck, Susanne S. Kim, Herbert W. Virgin IV,* and Samuel H. Speck*

Center for Immunology and Departments of Pathology and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110

Received 2 November 1998/Accepted 23 February 1999

The dynamics of the establishment of, and reactivation from, gammaherpesviruses latency has not been quantitatively analyzed in the natural host. Gammaherpesvirus 68 (gamma HV68) is a murine gammaherpesvirus genetically related to primate gammaherpesviruses that establishes a latent infection in infected mice. We used limiting dilution reactivation (frequency of cells reactivating gamma HV68 in vitro) and limiting dilution PCR (frequency of cells carrying gamma HV68 genome) assays to compare gamma HV68 latency in normal (C57BL/6) and B-cell-deficient (MuMT) mice. After intraperitoneal (i.p.) inoculation, latent gamma HV68 was detected in the spleen, bone marrow, and peritoneal cells. Both B-cell-deficient and C57BL/6 mice established latent infection in peritoneal cells after either i.p. or intranasal (i.n.) inoculation. In contrast, establishment of splenic latency was less efficient in B-cell-deficient than in C57BL/6 mice after i.n. inoculation. Analysis of reactivation efficiency (reactivation frequency compared to frequency of cells carrying gamma HV68 genome) revealed that (i) regardless of route or mouse strain, splenic cells reactivated gamma HV68 less efficiently than peritoneal cells, (ii) the frequency of cells carrying gamma HV68 genome was generally comparable over the course of infection between C57BL/6 and B-cell-deficient mice, (iii) between 28 and 250 days after infection, cells from B-cell-deficient mice reactivated gamma HV68 10- to 100-fold more efficiently than cells from C57BL/6 mice, (iv) at 7 weeks postinfection, B-cell-deficient mice had more genome-positive peritoneal cells than C57BL/6 mice, and (v) mixing cells (ratio of 3 to 1) that reactivated inefficiently with cells that reactivated efficiently did not significantly decrease reactivation efficiency. Consistent with a failure to normally regulate chronic gamma HV68 infection, the majority of infected B-cell-deficient mice died between 100 and 200 days postinfection. We conclude that (i) B cells are not required for establishment of gamma HV68 latency, (ii) there are organ-specific differences in the efficiency of gamma HV68 reactivation, (iii) B cells play a crucial role in regulating reactivation of gamma HV68 from latency, and (iv) B cells are important for controlling chronic gamma HV68 infection.

* Corresponding author. Mailing address: Department of Pathology, Box 8118, 660 S. Euclid Ave., St. Louis, MO 63110. Phone for Herbert W. Virgin IV: (314) 362-9223. Phone for Samuel H. Speck: (314) 362-0367. Fax: (314) 362-4096. E-mail for Herbert W. Virgin IV: virgin{at}pathology.wustl.edu. E-mail for Samuel H. Speck: speck{at}pathology.wustl.edu.

Journal of Virology, June 1999, p. 4651-4661, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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