MURINE CYTOMEGALOVIRUS-ASSOCIATED ARTERITIS

Unique inflammatory lesions affecting the ascending aorta and pulmonar y artery of BALB/c and C57BL/6 mice infected with murine cytomegalovir us (MCMV) were identified in a pilot and two subsequent experiments to characterize the potential effect of MCMV infection on diet-induced a therosclerotic lesions. Suckling BALB/c and C57BL/6 mice were inoculat ed 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 an d the dose of virus given. The conditions of MCMV exposure were progre ssively modified in the three experiments to increase the prevalence o f MCMV-associated inflammatory lesions in the pulmonary artery and aor ta. In the final experiment, in which suckling mice were inoculated at 9 days of age, MCMV-associated arteritic lesions had an observed prev alence at 8 weeks post-inoculation of 87.5% (7/8) in BALB/c mice on th e 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 bot h vessels were characterized by mononuclear cell infiltrates containin g CD3+, CD4+, and CD8+ lymphocytes. The cellular infiltrates were ofte n more intense on the adventitial surface and infiltrated into the ove rlying tunica media. The intima was infiltrated by mononuclear cell in filtrates that appeared to contain more macrophages and fewer lymphocy tes than did the adventitial infiltrates. Although the prevalence of i nflammatory lesions in the pulmonary artery and ascending aorta was in dependent of the atherogenic diet, lipid accumulation with formation o f foam cells within the inflammatory foci was clearly dependent on exp osure to the atherogenic diet in both strains. Total arterial lipid ac cretion in MCMV-inoculated mice of both strains was greater than that in their noninoculated counterparts because of the occurrence of infla mmation-associated lipid accretion in addition to the lipid accumulati on induced by the atherogenic diet alone. MCMV-associated arteritis ca n serve as a useful model to examine more fully the possible role of h uman cytomegalovirus infections in enhancing the pathogenesis of human atherosclerosis.