A BROAD-SPECTRUM CHEMOKINE ANTAGONIST ENCODED BY KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS

Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMI P-II, This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a numb er of both CC and CXC chemokine receptors, Binding of vMIP-II, however , was not associated with the normal, rapid mobilization of calcium fr om intracellular stores; instead, it blocked calcium mobilization indu ced 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 e ntry of human immunodeficiency virus (HIV) mediated through CCR3 and C CR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.