Kaposi’s sarcoma associated herpesvirus (KSHV, HHV-8) is the etiological agent of Kaposi’s sarcoma (KS), and is tightly associated with primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). The association of KS with immunosuppression such as AIDS makes it the most common malignancy in Africa today. Following infection the virus establishes a latency program that enables the virus to remain in the infected host for life, and latency is the major phase in herpes-virus associated malignancies. The Latency Associated Nuclear Antigen (LANA/ORF73) encoded by KSHV is one of the very few proteins expressed during latency. LANA is known to both activate and repress transcription in host cells to promote tumorigenesis, but the cellular factors that mediate LANA recruitment to specific cellular promoters and enhancers and the outcome of this recruitment on the chromatin state are still open questions. To begin investigate these questions we have performed ChIP assays with antibodies against several chromatin bound regulatory proteins and histone-marks at LANA bound promoters and enhancers. These studies detected dramatic changes in histone-marks following infection around LANA bound promoters and enhancers. In addition, we have analyzed the global effects of KSHV infection on the host cell CpG methylation and detected specific KSHV-mediated hypermethylation and hypomethylation sites. Integration of the ChIP results on LANA binding sites together with the methylome in KSHV-infection will help us to map the epigenetic modifications during KSHV infection and identify LANA partners in binding chromatin. This is a crucial step in understanding the molecular mechanism behind KSHV tumorigenesis.
