Herpesvirus-induced Atherosclerosis

Abstract

Atherosclerosis extraordinarily like the chronic human disease was reported as a consequence of Marek's disease herpesvirus (MDV) infection in specific pathogen-free (SPF) chickens. This arterial disease was induced not only in hypercholesterolemic but also in normocholesterolemic chickens by infection with MDV. Neither uninfected hypercholesterolemic nor normocholesterolemic SPF chickens developed this arterial disease. Repeated experiments have demonstrated that these results are reproducible. Grossly visible and microscopic atherosclerotic lesions were found in aortas, as well as coronary, brachiocephalic, celiac, gastric, and mesenteric arteries. Microscopic lesions were characterized by fibromuscular intimal thickening with fibrous caps overlying atheromatous change. Results of a pathogenesis experiment indicated that the earliest microscopic and gross arterial lesions occurred respectively at 1 and 3 mo post-MDV-infection. An additional important link established between infection and arterial lesions was the finding of specific MDV internal antigens in smooth muscle cells (SMC) of some medial layers of all arterial segments examined throughout the time span of lesion development (7 mo). Furthermore, lipid accumulations in arterial lesions of normocholesterolemic infected chickens and in cultured (chicken) arterial SMC suggest that a major mechanism in MDV atherosclerosis may be viral-induced alteration of cellular lipid metabolism. The distribution and morphologic character of MDV-atherosclerotic lesions closely resemble the chronic human arterial disease. Because humans are known to be widely and persistently infected with as many as five herpesviruses, these results may be particularly relevant to human atherosclerosis. Furthermore, since diabetes is an identified high risk factor of atherosclerosis, these findings may also be important in diabetes.