The Kaposi's Sarcoma-related Herpesvirus (KSHV)-encoded Chemokine vMIP-I is a Specific Agonist for the CC Chemokine Receptor (CCR)8

doi:10.1084/jem.189.12.1993

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J. Exp. Med., Volume 189, Number 12, June 21, 1999 1993-1998

The Kaposi's Sarcoma-related Herpesvirus (KSHV)-encoded Chemokine vMIP-I is a Specific Agonist for the CC Chemokine Receptor (CCR)8

By Michael J. Endres,^* Charles G. Garlisi, Hong Xiao, LiXin Shan,^§ and Joseph A. Hedrick^§

From the ^* Department of Antiviral Therapy, the Department of Allergy and Immunology, and the ^§ Department of Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey 07033

The Kaposi's sarcoma-related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiologic agent of Kaposi'ssarcoma and certain lymphomas. Although KSHV encodes several chemokinehomologues (viral macrophage inflammatory protein [vMIP]-I, -II,and -III), only vMIP-II has been functionally characterized. Wereport here that vMIP-I is a specific agonist for the CC chemokinereceptor (CCR)8 that is preferentially expressed on Th2 T cells.Y3 cells transfected with CCR8 produced a calcium flux in responseto vMIP-I and responded vigorously in in vitro chemotaxis assays.In competition binding experiments, the interaction of vMIP-Iwith CCR8 was shown to be specific and of high affinity. In contrastto its agonist activity at CCR8, vMIP-I did not interact withCCR5 or any of 11 other receptors examined. Furthermore, vMIP-Iwas unable to inhibit CCR5-mediated HIV infection. These findingssuggest that expression of vMIP-I by KSHV may influence the Th1/Th2balance of the host immuneresponse.

Key words: chemokines; cell trafficking; T helper cell type 1/T helper cell type 2; AIDS/HIV; inflammation

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