CHEMOKINES ACTIVATE KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS G-PROTEIN-COUPLED RECEPTOR IN MAMMALIAN-CELLS IN CULTURE

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8, a virus that appears to be involved in the pathogenesis of Kaposi's sarc oma and primary effusion lymphomas, encodes a G protein-coupled recept or (KSHV-GPCR) that exhibits constitutive signaling. In this report, w e show that two chemokines, interleukin 8 (IL-g) and growth-related pr otein-oc, activate KSHV-GPCR over constitutive levels. Moreover, as wi th human receptors, the integrity of the ELR motif of these chemokines is required for activation of KSHV-GPCR. Other residues that are requ ired for IL-8 binding to human chemokine receptors CXCR1 and CXCR2 are important for KSHV-GPCR activation also. Thus, it appears that the EL R binding site and other key domains of ELR chemokine activation have been preserved in the virus KSHV-GPCR. The results suggest that KSHV-G PCR originated from CXCR1 or CXCR2 and that activation of KSHV-GPCR by endogenous chemokines may affect the pathobiology of KSHV infection i n humans.