Kaposi’s Sarcoma-Associated Herpesvirus Open Reading

Kaposi’s sarcoma-associated herpesvirus (KSHV) open reading frame 50 (ORF50) encodes a viral tran-scriptional activator which stimulates the transcription of viral early and late genes of KSHV. Here we show that ORF50 represses transcriptional activity of p53 and p53-induced apoptosis through interaction with CREB binding protein (CBP). This inhibitory effect of ORF50 on the transcriptional activity of p53 was relieved by the addition of CBP. ORF50 mutants, which are defective in interaction with CBP, lost the inhibitory effects on p53. Our data provide a framework for delineating the regulatory mechanisms used by KSHV to modulate cellular transcription and the cell cycle. Kaposi’s sarcoma-associated herpesvirus (KSHV) has been identified as an important pathogen in Kaposi’s sarcoma (2, 4). DNA sequences of KSHV have been determined, and its in vitro culture system was recently developed (15, 16). The most important step in the KSHV life cycle may be the switch from latency to lytic replication. Upon chemical induction, KSHV produces immediate-early viral transcripts. These transcripts encode viral transcriptional activator proteins, such as ope