title: A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus.
abstract: Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors. Binding of vMIP-II, however, was not associated with the normal, rapid mobilization of calcium from intracellular stores; instead, it blocked calcium mobilization induced by endogenous chemokines. In freshly isolated human monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.
authors.affiliation: Laboratory for Molecular Pharmacology, Institute of Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: T N
authors.initials: TN
authors.lastname: Kledal
authors.forename: M M
authors.initials: MM
authors.lastname: Rosenkilde
authors.forename: F
authors.initials: F
authors.lastname: Coulin
authors.forename: G
authors.initials: G
authors.lastname: Simmons
authors.forename: A H
authors.initials: AH
authors.lastname: Johnsen
authors.forename: S
authors.initials: S
authors.lastname: Alouani
authors.forename: C A
authors.initials: CA
authors.lastname: Power
authors.forename: H R
authors.initials: HR
authors.lastname: Lüttichau
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: P R
authors.initials: PR
authors.lastname: Clapham
authors.forename: I
authors.initials: I
authors.lastname: Clark-Lewis
authors.forename: T N
authors.initials: TN
authors.lastname: Wells
authors.forename: T W
authors.initials: TW
authors.lastname: Schwartz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D015497:HIV-1 / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D011994:Recombinant Proteins; C108059:vMIP-II; D002118:Calcium