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Journal of Virology, May 2004, p. 5491-5499, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5491-5499.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Comparison of the Rta/Orf50 Transactivator Proteins of Gamma-2-Herpesviruses

Blossom Damania,1,2 Joseph H. Jeong,3 Brian S. Bowser,1,2 Scott M. DeWire,1,2 Michelle R. Staudt,3 and Dirk P. Dittmer1,3*

Department of Microbiology and Immunology,1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599,2 Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731043

Received 27 August 2003/ Accepted 20 January 2004

The viral immediate-early transactivator Rta/Orf50 is necessary and sufficient to initiate Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) reactivation from latently infected cells. Since Rta/Orf50 is conserved among all known gamma-2-herpesviruses, we investigated whether the murine gamma-68-herpesvirus (MHV-68) and rhesus monkey rhadinovirus (RRV) homologs can functionally substitute for KSHV Rta/Orf50. (i) Our comparison of 12 KSHV promoters showed that most responded to all three Rta/Orf50proteins, but three promoters (vGPCR, K8, and gB) responded only to the KSHV Rta/Orf50 transactivator. Overall, the activation of KSHV promoters was higher with KSHV Rta than with the RRV and MHV-68 Rta. (ii) Only the primate Rta/Orf50 homologs were able to interfere with human p53-depedent transcriptional activation. (iii) Transcriptional profiling showed that the KSHV Rta/Orf50 was more efficient than it's homologs in inducing KSHV lytic transcription from the latent state. These results suggest that the core functionality of Rta/Orf50 is conserved and independent of its host, but the human protein has evolved additional, human-specific capabilities.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 966-1191. Fax: (919) 962-8103. E-mail: dirkdittmer{at}MAC.com.

Journal of Virology, May 2004, p. 5491-5499, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5491-5499.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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