Report

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

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Science  12 Sep 1997:
Vol. 277, Issue 5332, pp. 1656-1659
DOI: 10.1126/science.277.5332.1656

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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.

  • * These authors contributed equally to this investigation.

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

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