Activation of cellular and heterologous promoters by the human herpesvirus 8 replication and transcription activator.
The key regulator of the switch from latent to lytic replication of the human herpesvirus 8 (HHV-8; KSHV) is the replication and transcription activator (Rta). The ability of Rta to regulate cellular gene expression was examined by transient transfection into cells that were not infected with HHV-8. Rta induced some, but not all, NF-kappa B-responsive reporters through mechanisms that did not involve activation of classic forms of NF-kappa B. Furthermore, transfection of the NF-kappa B subunit Rel A inhibited the ability of Rta to transactivate some but not all reporters. For example, Rel A inhibited the ability of Rta to transactivate the IL-6 promoter, but only when sequences upstream of the NF-kappa B site were present. The ability of Rel A to inhibit Rta-mediated transactivation was not dependent on a functional NF-kappa B site within the promoter, suggesting an indirect mechanism for inhibition. These studies suggest that Rta expression during lytic reactivation of HHV-8 would lead to expression of some cellular genes, including IL-6, whereas activation of NF-kappa B could inhibit some responses to Rta.
D001665:Binding Sites; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017930:Genes, Reporter; D006678:HIV / Q000235:genetics; D016322:HIV Enhancer; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
D017874:Immediate-Early Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014764:Viral Proteins; D015500:Chloramphenicol O-Acetyltransferase