Human Cytomegalovirus Causes Endothelial Injury Through the Ataxia Telangiectasia Mutant and p53 DNA Damage Signaling Pathways

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Abstract
Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV), a member of the herpes virus family, may play a role in the development of the disease. We previously showed that HCMV regulated endothelial apoptosis. In this study, we investigated the induction of apoptosis and signal transduction pathways regulating this process in HCMV-infected endothelial cells. As observed previously, HCMV induced a typical cytopathic effect in human aortic endothelial cells (HAECs), ie, the formation of single nucleated or multinucleated giant cells. Although infected HAECs were resistant to apoptosis at earlier stages of infection, they became apoptotic with prolonged infection as demonstrated by positive staining using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). This apoptotic process was mediated by the caspase-dependent mitochondrial apoptotic pathway as indicated by increased expression and cleavage of caspases 3 and 9 as well as increased e...