Regulation of Kaposi's Sarcoma-Associated Herpesvirus Lytic Gene Expression

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus associated with at least three human malignancies: Kaposi’s sarcoma, primary effusion lymphoma and multicentic Castleman’s disease. Like all herpesviruses, KSHV has both a latent and a lytic life cycle. The switch between latency and the lytic cycle is initiated by expression of a single transactivator encoded by open reading frame 50 (ORF50) of the viral genome. Expression of ORF50 protein alone in latently KSHV-infected cells is sufficient to disrupt viral latency and to drive the viral cascade to completion. Despite extensive studies on regulation of the ORF50 gene and its downstream lytic genes, the regulatory networks of these lytic-cycle genes are still not fully understood. Furthermore, little is known how many cellular genes can be activated by ORF50 protein and whether ORF50 protein has a repressive effect on gene expression. Since the ORF50 protein is the master controller of KSHV lytic reactivation, elucidating the regulation of expression, mode of action and downstream targets of ORF50 protein may provide novel insights into the viral lytic cycle and viral pathogenesis. The four specific aims are proposed in this project, which include: (1) determination of the role of YY1 protein in regulating KSHV reactivation; (2) investigation of the regulation of KSHV early lytic-cycle genes by ORF50; (3) identification of the cellular target genes of ORF50 protein; (4) determination of the ORF50-mediated transcriptional repression.

Project ID:PC9808-0552
External Project ID:NSC98-2320-B182-027-MY3