HUMAN CYTOMEGALOVIRUS-INFECTION UP-REGULATES INTERLEUKIN-8 GENE-EXPRESSION AND STIMULATES NEUTROPHIL TRANSENDOTHELIAL MIGRATION

Virus-induced alterations in the cellular expression of chemokines may be important in directing the migration of specific leucocyte subsets to sites of infection, thereby playing a pivotal role in viral pathog enesis. We show here that cytomegalovirus (CMV) infection of human fib roblasts resulted in significantly increased expression of the C-X-C o r alpha-chemokine interleukin-8 (IL-8), at both the mRNA and protein l evels. Increased IL-8 production was seen following infection with the high passage laboratory CMV strains AD169, Towne, or Davis, as well a s the low passage clinical CMV isolates Toledo or CIF. The increase in IL-8 production had functional consequences, as demonstrated by the a bility of supernatants from CMV-infected fibroblasts to significantly enhance neutrophil transendothelial migration. The latter was independ ent of alterations in adhesion molecule expression on the endothelial cells, and was abrogated by neutralizing antibodies specific for IL-8. Direct infection of endothelium with the endothelial cell-tropic CMV strain ClFE, also resulted in enhanced neutrophil transendothelial mig ration. Neutrophils play an important role in the dissemination of CMV throughout the body, and thus CMV-induced neutrophil recruitment woul d be expected to enhance CMV dissemination. Increased production of ch emokines in response to CMV infection could also disrupt the fine bala nce between a beneficial and a destructive immune response, thereby po tentially contributing to pathology.