The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/6/1993/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 12, June 21, 1999 1993-1998

Brief Definitive Reports

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

Michael J. Endres*, Charles G. Garlisi{ddagger}, Hong Xiao{ddagger}, LiXin Shan§, and Joseph A. Hedrick§

From the * Department of Antiviral Therapy, the {ddagger} 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's sarcoma and certain lymphomas. Although KSHV encodes several chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium flux in response to vMIP-I and responded vigorously in in vitro chemotaxis assays. In competition 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 examined. 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.

Key Words: chemokines • cell trafficking • T helper cell type 1/T helper cell type 2 • AIDS/HIV • inflammation

Address correspondence to Joseph A. Hedrick, Human Genome Research, K-15-1/1800, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033. Phone: 908-740-7408; Fax: 908-740-7664; E-mail: joseph.hedrick{at}spcorp.com

The authors would like to acknowledge a number of individuals for providing various cell lines: Dan Lundell, Paul Zavodny, Chung-Her Jenh, and Chuan Chu Chou (Schering-Plough Research Institute, Kenilworth, NJ) for CCR2, CCR6, CCR7, and CXCR3; Albert Zlotnik and Wei Wang (DNAX Research Institute, Palo Alto, CA) for CCR9; Shelby Umland and Himanshu Shah (Schering-Plough Research Institute) for CCR3; and Kevin Moore, Kurt Gish, and Christi Parham (DNAX Research Institute) for HCR/ L-CCR cells. In addition, we would like to acknowledge Sergio Lira and Frederick Monsma for helpful discussions regarding this work. Finally, thanks to Bahige Baroudy, M. Motasim Billah, Robert Egan, Francis Cuss, Marvin Bayne, and Catherine Strader for their support.

M.J. Endres and C.G. Garlisi contributed equally to this manuscript.


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