Activation of Cellular and Heterologous Promoters by the Human Herpesvirus 8 Replication and Transcription Activator

• Published in: Virology (New York, N.Y.) N.Y.), 2002-09, Vol.301 (2), p.293-304
• Main Authors: Roan, Florence, Inoue, Naoki, Offermann, Margaret K.
• Format: Article
• Language: English
• Subjects: Binding Sites; Cell Line, Transformed; cellular promoters; Chloramphenicol O-Acetyltransferase - genetics; Genes, Reporter; HeLa Cells; Herpesvirus 8, Human - metabolism; Herpesvirus 8, Human - physiology; HIV - genetics; HIV Enhancer; human herpesvirus 8; Humans; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Kaposi's sarcoma herpesvirus; lytic reactivation; NF-kappa B - metabolism; NF-κB; ORF 50; Promoter Regions, Genetic; Response Elements; Rta; Trans-Activators - genetics; Trans-Activators - metabolism; transcription; Transcription Factor RelA; Transcriptional Activation; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Replication - physiology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2002.1582

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-κB-responsive reporters through mechanisms that did not involve activation of classic forms of NF-κB. Furthermore, transfection of the NF-κB 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-κB site were present. The ability of Rel A to inhibit Rta-mediated transactivation was not dependent on a functional NF-κB 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-κB could inhibit some responses to Rta.