Comparison of the Rta/Orf50 transactivator proteins of gamma-2-herpesviruses.
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.
Damania
Blossom
B
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jeong
Joseph H
JH
Bowser
Brian S
BS
DeWire
Scott M
SM
Staudt
Michelle R
MR
Dittmer
Dirk P
DP
D000595:Amino Acid Sequence; D000818:Animals; D019288:Herpesvirus 8, Human / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018144:Rhadinovirus / Q000737:chemistry* / Q000502:physiology; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*; D014775:Virus Activation
D017874:Immediate-Early Proteins; C116742:ORF 50 transactivator; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins