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Journal of Virology, August 2008, p. 7688-7699, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02689-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Establishment of B-Cell Lines Latently Infected with Reactivation-Competent Murine Gammaherpesvirus 68 Provides Evidence for Viral Alteration of a DNA Damage-Signaling Cascade{triangledown}

J. Craig Forrest and Samuel H. Speck*

The Emory Vaccine Center and Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 18 December 2007/ Accepted 15 May 2008

Gammaherpesvirus 68 ({gamma}HV68, or MHV68) is a naturally occurring rodent pathogen that replicates to high titer in cell culture and is amenable to in vivo experimental evaluation of viral and host determinants of gammaherpesvirus disease. However, the inability of MHV68 to transform primary murine B cells in culture, the absence of a robust cell culture latency system, and the paucity of MHV68-positive tumor cell lines have limited an understanding of the molecular mechanisms by which MHV68 modulates the host cell during latency and reactivation. To facilitate a more complete understanding of viral and host determinants that regulate MHV68 latency and reactivation in B cells, we generated a recombinant MHV68 virus that encodes a hygromycin resistance protein fused to enhanced green fluorescent protein as a means to select cells in culture that harbor latent virus. We utilized this virus to infect the A20 murine mature B-cell line and evaluate reactivation competence following treatment with diverse stimuli to reveal viral gene expression, DNA replication, and production of progeny virions. Comparative analyses of parental and infected A20 cells indicated a correlation between infection and alterations in DNA damage signaling following etoposide treatment. The data described in this study highlight the potential utility of this new cell culture-based system to dissect molecular mechanisms that regulate MHV68 latency and reactivation, as well as having the potential of illuminating biochemical alterations that contribute to gammaherpesvirus pathogenesis. In addition, such cell lines may be of value in evaluating targeted therapies to gammaherpesvirus-related tumors.

* Corresponding author. Mailing address: Emory Vaccine Center, 1462 Clifton Road, Atlanta, GA 30322. Phone: (404) 727-7665. Fax: (404) 712-9736. E-mail: sspeck{at}emory.edu

{triangledown} Published ahead of print on 21 May 2008.

Journal of Virology, August 2008, p. 7688-7699, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.02689-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gargano, L. M., Forrest, J. C., Speck, S. H. (2009). Signaling through Toll-Like Receptors Induces Murine Gammaherpesvirus 68 Reactivation In Vivo. J. Virol. 83: 1474-1482 [Abstract] [Full Text]  
  • Gray, K. S., Allen, R. D. III, Farrell, M. L., Forrest, J. C., Speck, S. H. (2009). Alternatively Initiated Gene 50/RTA Transcripts Expressed during Murine and Human Gammaherpesvirus Reactivation from Latency. J. Virol. 83: 314-328 [Abstract] [Full Text]  
  • Jarousse, N., Chandran, B., Coscoy, L. (2008). Lack of Heparan Sulfate Expression in B-Cell Lines: Implications for Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus 68 Infections. J. Virol. 82: 12591-12597 [Abstract] [Full Text]  


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