The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine nu MIP-Iis a specific agonist for the CC chemokine receptor (CCR)8

The Kaposi's sarcoma-related herpesvirus (KSHV), also designated human herp esvirus 8, is the presumed etiolgic agent of Kaposi's sarcoma and certain l ymphomas. Although KSHV encodes several chemokine homologues (viral macroph age inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been fu nctionally characterized. We report here that vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8 that is preferentially expressed on Th 2 T cells. Y3 cells transfected with CCR8 produced a calcium nux in respons e to VMIP-I and responded vigorously in in vitro chemotaXis assays. In comp etition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other receptors exami ned. Furthermore, VMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.