Human CMV infection of endothelial cells induces an angiogenic response through viral binding to EGF receptor and beta1 and beta3 integrins.
Human cytomegalovirus (HCMV) infection is associated with atherosclerosis, transplant vascular sclerosis, and coronary restenosis. A common theme in these vascular diseases is an increased rate of angiogenesis. Angiogenesis is a complex biological process mediated by endothelial cell (EC) proliferation, migration, and morphogenesis. Although angiogenesis is a normal process in the host, its dysregulation, after viral infection or injury to the vessel wall, is associated with plaque development in atherosclerotic patients. We now document that HCMV infection results in increased EC proliferation, motility, and capillary tube formation. The observed HCMV-induced angiogenic response depended on viral binding to and signaling through the beta(1) and beta(3) integrins and the epidermal growth factor receptor, via their ability to activate the phosphatidylinositol 3-kinase and the mitogen-activated protein kinase signaling pathways. Because a proangiogenic response drives the neovascularization observed in atherosclerotic disease, our findings identify a possible mechanism for how HCMV infection contributes to vascular disease.
Bentz
Gretchen L
GL
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Yurochko
Andrew D
AD
D001665:Binding Sites; D002465:Cell Movement; D049109:Cell Proliferation; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000473:pathology / Q000821:virology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D014652:Vascular Diseases / Q000209:etiology; D053585:Virus Attachment
D019012:Integrin beta1; D039661:Integrin beta3; D011956:Receptors, Cell Surface; D066246:ErbB Receptors