Distinct chemotactic and angiogenic activities of peptides derived from Kaposi's sarcoma virus encoded chemokines

The vMIPs are chemokine-like proteins expressed by the Kaposi's sarcoma-ass ociated herpesvirus (KSHV/HHV8) during the lytic phase of viral infection. vMIP-I activates CCR8, a chemokine receptor expressed by Th2 lymphocytes an d cultured monocytes. vMIP-II is an agonist for CCR3, a receptor expressed by eosinophils, and an antagonist for several other chemokine receptors. Bo th are highly angiogenic in the chick chorio-allantoic membrane. We designe d and tested three 26-mer peptides, derived from vMIP-I (pK-I), from vMIP-I I (pK-II) and from the control MIP-1 alpha (pM), spanning key residues of c hemokines. pK-I, pK-II and pM all were able to activate a strong chemotacti c response in monocytes, higher than parental vMIP-I and II. This correspon ded to induction of calcium fluxes in these cells, typical of chemokines. I nterestingly, pK-II and pM were also active on PMN neutrophils. In vivo stu dies (matrigel sponge and rabbit cornea models) showed that pK-I retains th e strong angiogenic potential exerted by vMIP-I, while pK-II and pM induced an inflammatory response, probably mediated by PMN recruitment. Our observ ations indicate that chemokine-derived peptides can show biological activit y at pharmacological concentrations. pK-I, in particular, displays the angi ogenic activity of full-length vMIP-I, while all peptides appear to have ac quired additional properties, stimulating new cellular targets.