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Science 12 September 1997:
Vol. 277. no. 5332, pp. 1656 - 1659
DOI: 10.1126/science.277.5332.1656
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Reports

A Broad-Spectrum Chemokine Antagonist Encoded by Kaposi's Sarcoma-Associated Herpesvirus

Thomas N. Kledal, * Mette M. Rosenkilde, * Florence Coulin, Graham Simmons, Anders H. Johnsen, Sami Alouani, Christine A. Power, Hans R. Lüttichau, Jan Gerstoft, Paul R. Clapham, Ian Clark-Lewis, Timothy N. C. Wells, dagger Thue W. Schwartz dagger

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.

T. N. Kledal, M. M. Rosenkilde, T. W. Schwartz, Laboratory for Molecular Pharmacology, Institute of Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
A. H. Johnsen, Department of Clinical Biochemistry; H. R. Lüttichau and J. Gerstoft, Department of Infectious Diseases, Rigshospitalet, DK-2100 Copenhagen, Denmark.
G. Simmons and P. R. Clapham, Section of Virology, Chester Beatty Laboratories, The Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK.
I. Clark-Lewis, Biomedical Research Center, University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada.
F. Coulin, S. Alouani, C. A. Power, T. N. C. Wells, Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development S.A., 1228 Plan-les-Ouates, Geneva, Switzerland.
*   These authors contributed equally to this investigation.

dagger    To whom correspondence should be addressed. E-mail: schwartz{at}molpharm.dk or tncw5312{at}ggr.co.uk

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The Viral Chemokine Macrophage Inflammatory Protein-II Is a Selective Th2 Chemoattractant.
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A Broad Range of Chemokine Receptors Are Used by Primary Isolates of Human Immunodeficiency Virus Type 2 as Coreceptors with CD4.
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The CCR5 receptor acts as an alloantigen in CCR5Delta 32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies.
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Comprehensive Mapping of Poxvirus vCCI Chemokine-binding Protein. EXPANDED RANGE OF LIGAND INTERACTIONS AND UNUSUAL DISSOCIATION KINETICS.
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