Herpesvirus infection prevents activation of cytoplasmic cholesteryl esterase in arterial smooth muscle cells.
Herpesvirus infection has been shown to alter the cholesteryl ester cycle in avian arterial smooth muscle cells, resulting in cytoplasmic cholesteryl ester accumulation (Hajjar, D. P., Falcone, D. J., Fabricant, C. G., and Fabricant, J. (1985) J. Biol. Chem. 260, 6124-6128). In this study, we attempted to define some of the regulatory mechanisms associated with the control of cytoplasmic cholesteryl esterase in Marek's disease herpesvirus (MDV)-infected cells. We found that cholesteryl esterase activity in MDV-infected cells could not be activated by dibutyryl cyclic AMP, dibutyryl cyclic AMP added together with protein kinase, or agonists of adenylate cyclase. Activation of cytoplasmic cholesteryl esterase activity occurred in uninfected cells and in cells infected with a control virus, turkey herpesvirus. Furthermore, the rate of cholesterol efflux from arterial smooth muscle cells challenged with dibutyryl cyclic AMP was unchanged in MDV-infected cells as compared to uninfected or turkey herpesvirus-infected cells in which efflux was increased. We propose that the reduced cytoplasmic cholesteryl esterase activity in lipid-laden, herpesvirus-infected cells is due partly to its inability to be activated by the cyclic AMP-protein kinase mechanism. This may contribute to the pathologic changes seen in MDV-infected arterial cells, including accumulation of intracellular cholesteryl esters.
D000818:Animals; D001011:Aorta / Q000201:enzymology; D003994:Bucladesine / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002645:Chickens; D002784:Cholesterol / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D008381:Herpesvirus 2, Gallid / Q000235:genetics*; D008297:Male; D008380:Marek Disease / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D013047:Specific Pathogen-Free Organisms; D002787:Sterol Esterase / Q000037:antagonists & inhibitors*
D003994:Bucladesine; D002784:Cholesterol; D002265:Carboxylic Ester Hydrolases; D002787:Sterol Esterase