The Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 is associated with malignancies such as Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. These tumors primarily occur in immune suppressed individuals, including organ transplant recipients and AIDS patients. In infected cells, KSHV is primarily latent and the viral DNA is maintained as a multiple copy extrachromosomal element or episome. KSHV latency-associated nuclear antigen (LANA) colocalizes with mitotic chromosomes and KSHV DNA. LANA is required for KSHV DNA with a specific cis-acting sequence to persist as an episome in infected cells. This data is consistent with LANA tethering KSHV episomes to chromosomes to mediate efficient segregation of KSHV episomes to progeny cells. Recent work shows that LANA is phosphorylated. The objectives of this proposal are (i) to characterize LANA's phosphorylation status in KSHV infected cells, (ii) to define the residues of LANA that are phosphorylated; (iii) to assess the effect of phosphorylation on LANA's functions. These experiments may identify targets for pharmacological intervention in the treatment of Kaposi's sarcoma and KSHV-associated malignancies.
