MURINE CYTOMEGALOVIRUS-ASSOCIATED ARTERITIS

Unique inflammatory lesions affecting the ascending aorta and pulmonary artery of BALB/c and C57BL/6 mice infected with murine cytomegalovirus (MCMV) were identified in a pilot and two subsequent experiments to characterize the potential effect of MCMV infection on diet-induced atherosclerotic lesions. Suckling BALB/c and C57BL/6 mice were inoculated with MCMV and subsequently fed either a commercial mouse diet or a synthetic atherogenic diet from weaning. The three experiments varied with respect to the age of the mice at the time of MCMV inoculation and the dose of virus given. The conditions of MCMV exposure were progressively modified in the three experiments to increase the prevalence of MCMV-associated inflammatory lesions in the pulmonary artery and aorta. In the final experiment, in which suckling mice were inoculated at 9 days of age, MCMV-associated arteritic lesions had an observed prevalence at 8 weeks post-inoculation of 87.5% (7/8) in BALB/c mice on the normal diet and 100% (8/8) in C57BL/6 mice on the normal diet and in both strains on the atherogenic diet. The inflammatory lesions in both vessels were characterized by mononuclear cell infiltrates containing CD3+, CD4+, and CD8+ lymphocytes. The cellular infiltrates were often more intense on the adventitial surface and infiltrated into the overlying tunica media. The intima was infiltrated by mononuclear cell infiltrates that appeared to contain more macrophages and fewer lymphocytes than did the adventitial infiltrates. Although the prevalence of inflammatory lesions in the pulmonary artery and ascending aorta was independent of the atherogenic diet, lipid accumulation with formation of foam cells within the inflammatory foci was clearly dependent on exposure to the atherogenic diet in both strains. Total arterial lipid accretion in MCMV-inoculated mice of both strains was greater than that in their noninoculated counterparts because of the occurrence of inflammation-associated lipid accretion in addition to the lipid accumulation induced by the atherogenic diet alone. MCMV-associated arteritis can serve as a useful model to examine more fully the possible role of human cytomegalovirus infections in enhancing the pathogenesis of human atherosclerosis.