© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Effect of cytomegalovirus immediate early gene products on endothelial cell gene activity
aDepartment of Human Genetics and Molecular Medicine, Sackler School of Medicine Tel Aviv University, Tel Aviv, Israel
bBIEX, Inc., Dublin, CA, USA
cDepartment of Cell Biology, Research Institute of the Cleveland Clinic Foundation, Cleveland, OH, USA
* Corresponding author. Present address: Danek Gertner Institute of Human Genetics Sheba Medical Center, Tel-Hashomer, 52621 Israel. Tel.: +972-3-530-3974; fax: +972-3-530-2914 guetta{at}post.tau.ac.il
Objective: Cytomegalovirus (CMV) infection or reactivation from latency in vascular cells have been shown to contribute to atherosclerosis. CMV-infected endothelial cells (ECs) exhibit enhanced adhesion and procoagulant properties, changes compatible with processes observed in atherogenesis. The major immediate early promoter drives immediate early gene transcription. Immediate early (IE) gene products, IE72 and IE84, function as transcription factors and thereby influence expression of cellular genes, in permissive cells as well as in abortive infections, in which viral activity is limited to immediate early expression. ECs have been shown to harbor latent CMV, support abortive CMV infection and, under certain conditions, are permissive to productive viral infection. The objective of this study was to determine whether immediate early expression alone (in the absence of further progression of the virus life-cycle) results in the activation of EC genes associated with atherogenesis. Methods: The study was conducted in an in vitro transient transfection system in human and bovine vascular ECs, with CMV immediate early gene expression vectors and plasmids containing promoter sequences of adhesion molecule, growth factor and viral promoters driving the transcription of reporter genes. Results: CMV immediate early gene expression resulted in an increase in monocyte adhesion to ECs and in the relative promoter activities of cellular growth factor and adhesion molecule genes. In addition, the viral major immediate early promoter was regulated in EC by thrombin and the immediate early gene products. Conclusion: These results infer 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 further activation of CMV activity.
KEYWORDS Atherosclerosis; Cell culture/isolation; Endothelial factors; Gene expression; Infection/inflammation
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