Effect of cytomegalovirus immediate early gene products on endothelial cell gene activity

Objective: Cytomegalovirus (CMV) infection or reactivation from latency in vascular cells have been shown to contribute to atherosclerosis. CMV-infect ed endothelial cells (ECs) exhibit enhanced adhesion and procoagulant prope rties, changes compatible with processes observed in atherogenesis. The maj or immediate early promoter drives immediate early gene transcription. imme diate early (IE) gene products, IE72 and IE84, function as transcription fa ctors and thereby influence expression of cellular genes, in permissive cel ls as well as in abortive infections, in which viral activity is limited to immediate early expression. ECs have been shown to harbor latent CMV, supp ort abortive CMV infection and, under certain conditions, are permissive to productive viral infection. The objective of this study was to determine w hether immediate early expression alone (in the absence of further progress ion of the virus life-cycle) results in the activation of EC genes associat ed with atherogenesis. Methods: The study was conducted in an in vitro tran sient transfection system in human and bovine vascular ECs, with CMV immedi ate early gene expression vectors and plasmids containing promoter sequence s of adhesion molecule, growth factor and viral promoters driving the trans cription of reporter genes. Results: CMV immediate early gene expression re sulted in an increase in monocyte adhesion to ECs and in the relative promo ter activities of cellular growth factor and adhesion molecule genes. In ad dition, the viral major immediate early promoter was regulated in EC by thr ombin and the immediate early gene products. Conclusion: These results infe r the possible existence of a positive feedback mechanism in the developing atherosclerotic lesion, in which enhanced immediate early gene expression leads to subsequent activation of EC genes, which might in turn result in f urther activation of CMV activity. (C) 2001 Elsevier Science B.V. Ail right s reserved.