HUMAN HERPESVIRUS KSHV ENCODES A CONSTITUTIVELY ACTIVE G-PROTEIN-COUPLED RECEPTOR-LINKED TO CELL-PROLIFERATION

Kaposi's sarcoma-associated herpesvirus (KSHV, also known as human her pesvirus 8, or HHV 8) is a virus that is consistently present in Kapos i's sarcoma(1,2) and in primary-effusion (body-cavity-based) lymphomas (3), malignancies that occur frequently, but not exclusively in AIDS p atients. KSHV is a gamma herpesvirus with homology to herpesvirus Saim iri and Epstein-Barr virus(1,4), both of which can transform lymphocyt es(5). Cloning of a KSHV genome fragment revealed the presence of an o pen reading frame encoding a putative G-protein-coupled receptor(6) th at is homologous to a G-protein-coupled receptor encoded by herpesviru s Saimiri(7,8) and to human interleukin-8 receptors(9,10). Here we sho w that the KSHV G-protein-coupled receptor is a bona fide signalling r eceptor which has constitutive (agonist-independent) activity in the p hosphoinositide-inositoltrisphosphate-protein kinase C pathway. Furthe rmore, the KSHV G-protein-coupled receptor stimulates cellular prolife ration, making it a candidate viral oncogene.