Infection of vascular endothelial cells with human cytomegalovirus under fluid shear stress reveals preferential entry and spread of virus in flow conditions simulating atheroprone regions of the artery.
Atherosclerosis is a major pathogenic factor in cardiovascular diseases, which are the leading cause of mortality in developed countries. While risk factors for atherosclerosis tend to be systemic, the distribution of atherosclerotic plaques within the vasculature is preferentially located at branch points and curves where blood flow is disturbed and shear stress is low. It is now widely accepted that hemodynamic factors can modulate endothelial gene expression and function and influence the pathophysiological changes associated with atherosclerosis. Human cytomegalovirus (HCMV), a ubiquitous pathogen, has long been proposed as a risk factor for atherosclerosis. To date, the role of HCMV in atherogenesis has been explored only in static conditions, and it is not known how HCMV infection is influenced by the physiological context of flow. In this study, we utilized a parallel-plate flow system to simulate the effects of shear stresses in different regions of the vasculature in vitro. We found that endothelial cells cultured under low shear stress, which simulates the flow condition of atheroprone regions in vivo, are more permissive to HCMV infection than cells experiencing high shear stress or static conditions. Cells exposed to low shear stress show increased entry of HCMV compared to cells exposed to high shear stress or static conditions. Viral structural gene expression, viral titers, and viral spread are also enhanced in endothelial cells exposed to low shear stress. These results suggest that hemodynamic factors modulate HCMV infection of endothelial cells, thus providing new insights into the induction/acceleration of atherosclerosis by HCMV.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.
Jenny B
JB
DuRose
Julie
J
Li
Shu
S
Chien
Deborah H
DH
Spector
D001158:Arteries / Q000821:virology*; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D017931:DNA Primers; D004279:DNA, Viral / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000821:virology*; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D008561:Membrane Fusion; D046529:Microscopy, Electron, Transmission; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D004279:DNA, Viral