The Oncogenic G Protein-Coupled Receptor of KSHV as a Candidate Pharmacologic Target

摘要

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV 8), is a gammaherpesvirus consistently associated with KS (Classic and AIDS-associated), the primary effusion lymphomas (PEL), and multicentric Castleman's disease. Sequence homology to Epstein-Barr virus (EBV) and Herpesvirus saimiri (HVS), together with a wide armory of pirated cell-homologous genes involved in crucial biological events all suggest that KSHV may play an active role in the pathogenesis of these malignancies. One such pirated gene (ORF 74) is a homolog of the G protein-coupled receptor (GPCR) of HVS (ECRF3) and the human interleukin-8 (IL-8) receptors (CXCR1 and CXCR2). Studies characterizing the biological activity of this viral GPCR are reviewed and their implications for the transforming and/or pathogenic potential of KSHV are discussed in this chapter.