Cytomegalovirus induces sialyl Lewis(x) and Lewis(x) on human endothelial cells

Background. Cytomegalovirus (CMV) is the primary viral cause of complicatio ns in transplant recipients. We sought to understand the mechanisms of its dissemination and induction of vascular disease, which may lead to transpla nt complications. Sialyl Lewis(x) (sLe(x)) and Lewis(x) (Le(x)) are known f or their roles in mediating cell adhesion and as tumor-associated carbohydr ate antigens, Herein we explore whether CMV induces surface expression of t hese important molecules in endothelial cells (EC). Methods. Flow cytometry was used to detect surface expression of sLe(x) and Le(x) on CMV-infected human umbilical vein endothelial cells (HUVEC), with or without ultraviolet inactivation of the virus, To elucidate mechanisms of CMV-mediated induction, mRNA coding for predominant HUVEC sialyltransfer ases (ST) and fucosyltransferases (FT), key enzymes in sLe(x) and Le(x) syn thesis, was analyzed by Northern blot. Dual immunohistochemical staining fo r sLe(x) and Le(x) expression of human colon and placental tissue was perfo rmed to investigate in vivo relevance. Results. sLe(x) expression on CMV-infected HUVEC was strongly up-regulated by 8 days after inoculation. Le(x) expression was detectable earlier and in creased steadily over time. In contrast, ultraviolet-inactivated CMV did no t induce expression of these molecules. Northern blot assays demonstrated h igher levels of important EC glycosyltransferases ST-IV, FT-III, and FT-IV in CMV-infected EC. Finally, high levels of sLe(x) and Le(x) were expressed in CMV-infected EC in vivo. Conclusions. Given the known biologic functions of sLe(x) and Le(x), we sug gest that CMV induction of these molecules may have widespread consequences ranging from CMV dissemination to induction of CMV-associated vascular dis ease, including thrombosis.