Experimental infection with bovine herpesvirus-4 enhances atherosclerotic process in rabbits

An association of herpesvirus and atherosclerosis has been suggested by seroepidemiologic studies and detection of the virus in arterial tissues. To facilitate the studies of the pathogenic role of herpesvirus in atherosclerosis, we established a rabbit model of atherosclerosis with bovine herpesvirus type-4 (BHV-4). Forty New Zealand White rabbits were randomly divided into six groups. Groups 1, 2, and 3 were inoculated iv with BHV-4 and control Groups 4, 5, and 6 with normal saline. Groups I and 4 were fed a regular diet throughout the experiment; Groups 2 and 5 were fed a diet supplemented with 2% cholesterol for 3 weeks starting at 3 weeks postinoculation; and Groups 3 and 6 with a diet supplemented with 2% cholesterol for 6 weeks starting at 3 days postinoculation. Extensive atherosclerotic lesions in Groups 2, 3, and 6, and small lesions in two rabbits in Group 1 were observed, but no obvious lesions were observed in Groups 4 and 5. BHV-4 DNA was demonstrated by polymerase chain reaction and liquid hybridization in aortic sections, various tissue samples, and peripheral blood mononuclear cells of all infected rabbits. Our studies demonstrated that BHV-4 can accelerate the atherosclerotic process in rabbits, and that experimental infection of rabbits with BHV-4 can be a useful atherosclerosis model.