Viral G Protein–Coupled Receptor and Kaposi's Sarcoma: A Model of Paracrine Neoplasia?

The most recently identified human herpesvirus, Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), has been found to be a necessary, although perhaps not sufficient, etiologic agent for all forms of KS 1,2. This virus is also invariably present in a rare subset of malignant lymphomas, primary effusion lymphomas (PELs), and in a significant percentage of patients with multicentric Castleman's disease, an angiolymphoproliferative disorder 3,4. Both KS and PEL occur more frequently, but not exclusively, in HIV-infected individuals, and all cases of HIV-related multicentric Castleman's disease are infected with KSHV. These findings suggest an important role of immunosuppression and HIV infection in KSHV-mediated pathogenesis. Although it remains controversial whether KS is a malignant neoplasm, KS lesions probably evolve from a reactive, inflammatory/angioproliferative process into true clonal cancers. Thus, KS is generally...