) Kaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, and HIV infection is a strong risk factor for KS development. However, epidemiologic data indicate that HIV is not the sole determinant of KS risk and point to a sexually transmitted factor as being important in KS pathogenesis. Recently, the genome of a novel herpesvirus called KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has been closely linked to KS tumors; this virus has been suggested as a candidate for the proposed cofactor. A complete understanding of the potential contribution(s) of KSHV/HHS8 to KS tumorigenesis will require a detailed knowledge of the viral genes expressed in the tumor. The applicant has cloned the entire genome of KSHV/HHV8, developed a cell culture system for virus production, and identified two abundant viral transcripts expressed in KS tumor cells. These RNAs are highly distinctive and are not closely analogous to known gene products of related gamma herpesviruses. This project will further characterize these viral genes and identify and characterize additional viral genes expressed in KS. The protein products of these genes will be characterized biochemically and functionally, with particular attention to their potential to influence cellular growth control and differentiation. These studies should provide new molecular clues to the potential roles of KSHV/HHV8 in KS and could identify new targets for therapeutic intervention in the future.
