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Journal of Virology, September 2004, p. 9215-9223, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9215-9223.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Generation of a Latency-Deficient Gammaherpesvirus That Is Protective against Secondary Infection

Tammy M. Rickabaugh,1 Helen J. Brown,2 DeeAnn Martinez-Guzman,1 Ting-Ting Wu,2 Leming Tong,2 Fuqu Yu,2 Steven Cole,1,3,4 and Ren Sun1,2,4,5*

Department of Molecular and Medical Pharmacology,2 Department of Medicine,3 UCLA AIDS Institute,4 Jonsson Comprehensive Cancer Center,5 Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California1

Received 6 January 2004/ Accepted 22 April 2004

Kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus-68 (MHV-68) establish latent infections and are associated with various types of malignancies. They are members of the gamma-2 herpesvirus subfamily and encode a replication and transcriptional activator, RTA, which is necessary and sufficient to disrupt latency and initiate the viral lytic cycle in vitro. We have constructed a recombinant MHV-68 virus that overexpresses RTA. This virus has faster replication kinetics in vitro and in vivo, is deficient in establishing latency, exhibits a reduction in the development of a mononucleosis-like disease in mice, and can protect mice against challenge by wild-type MHV-68. The present study, by using MHV-68 as an in vivo model system, demonstrated that RTA plays a critical role in the control of viral latency and suggests that latency is a determinant of viral pathogenesis in vivo.

* Corresponding author. Mailing address: Department of Molecular and Medical Pharmacology, School of Medicine, 23-170 CHS, University of California at Los Angeles, 10833 Le Conte Ave., Los Angeles, CA 90095-1735. Phone: (310) 794-5557. Fax: (310) 825-6267. E-mail: rsun{at}mednet.ucla.edu.

Journal of Virology, September 2004, p. 9215-9223, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9215-9223.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wu, T.-T., Park, T., Kim, H., Tran, T., Tong, L., Martinez-Guzman, D., Reyes, N., Deng, H., Sun, R. (2009). ORF30 and ORF34 Are Essential for Expression of Late Genes in Murine Gammaherpesvirus 68. J. Virol. 83: 2265-2273 [Abstract] [Full Text]  
  • Kayhan, B., Yager, E. J., Lanzer, K., Cookenham, T., Jia, Q., Wu, T.-T., Woodland, D. L., Sun, R., Blackman, M. A. (2007). A Replication-Deficient Murine {gamma}-Herpesvirus Blocked in Late Viral Gene Expression Can Establish Latency and Elicit Protective Cellular Immunity. J. Immunol. 179: 8392-8402 [Abstract] [Full Text]  
  • Rickabaugh, T. M., Brown, H. J., Wu, T.-T., Song, M. J., Hwang, S., Deng, H., Mitsouras, K., Sun, R. (2005). Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 RTA Reactivates Murine Gammaherpesvirus 68 from Latency. J. Virol. 79: 3217-3222 [Abstract] [Full Text]  


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