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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.
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.
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