Cytomegalovirus encodes a potent alpha chemokine

Cytomegalovirus is a widespread opportunistic pathogen affecting immunocomp romised individuals in whom neutrophils may mediate virus dissemination and contribute to progression of disease. Recent sequence analysis suggests th at genes absent or altered in attenuated strains may influence pathogenesis . We have found two genes, UL146 and UL147, whose products have sequence si milarity to or (CXC) chemokines, UL146 encodes a protein, designated vCXC-1 , that is a 117-aa glycoprotein secreted into the culture medium as a late gene product, where its presence correlates with the ability to attract hum an neutrophils. Recombinant vCXC-1 is a fully functional chemokine, inducin g calcium mobilization, chemotaxis, and degranulation of neutrophils. High- affinity vCXC-1 binding is shown to be mediated via CXCR2, but not CXCR1. v CXC-1 exhibits a potency approaching that of human IL-8. As the first examp le of a virus-encoded alpha chemokine, vCXC-1 may ensure the active recruit ment of neutrophils during cytomegalovirus infection, thereby providing for efficient dissemination during acute infection and accounting for the prom inence of this leukocyte subset in cytomegalovirus disease.