CYTOMEGALOVIRUS-INFECTED ENDOTHELIAL-CELLS RECRUIT NEUTROPHILS BY THESECRETION OF C-X-C CHEMOKINES AND TRANSMIT VIRUS BY DIRECT NEUTROPHIL-ENDOTHELIAL CELL CONTACT AND DURING NEUTROPHIL TRANSENDOTHELIAL MIGRATION

Infection of endothelial cells with an endothelial cell-tropic clinica l isolate of cytomegalovirus (CMV), C1FE, induced enhanced production of the neutrophil chemoattractant C-X-C chemokines interleukin-8 and G RO alpha, Infected endothelial cell supernatants induced neutrophil ch emotaxis in a transendothelial migration assay. Neutrophils acquired t he CMV structural protein pp65 following either coculture with infecte d endothelial cells or transmigration through infected endothelium. Th e lack of CMV p72 expression in the neutrophils indicated that viral r eplication had not occurred in these cells. Of importance, neutrophils acquired infectious CMV during transmigration across infected endothe lium and were subsequently able to transmit infectious virus to fibrob lasts. Thus, CMV-infected endothelial cells can recruit neutrophils by the secretion of C-X-C chemokines and can transmit the virus to them by direct cell-to-cell contact and during neutrophil transendothelial migration, suggesting that the neutrophil-endothelial cell interaction plays an important role in virus dissemination in vivo.