title: The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8.
abstract: 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.
authors.affiliation: Department of Antiviral Therapy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Endres
authors.forename: C G
authors.initials: CG
authors.lastname: Garlisi
authors.forename: H
authors.initials: H
authors.lastname: Xiao
authors.forename: L
authors.initials: L
authors.lastname: Shan
authors.forename: J A
authors.initials: JA
authors.lastname: Hedrick
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018925:Chemokines / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D051379:Mice; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000209:etiology; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection; D014764:Viral Proteins
chemical_list: C103330:CCR8 protein, human; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D014764:Viral Proteins; C108459:vMIP-1 protein, Human herpesvirus 8; D002118:Calcium