Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse

Background-Human herpesviruses have been implicated but not proven to be in volved in the etiology of atherosclerosis. To determine whether there is a causal relationship, the effect of herpesvirus infection on the development of atherosclerosis was assessed in the apolipoprotein E-deficient (apoE-/- ) mouse. Methods and Results-In the present study, 3- to 4-week-old apoE-/- mice wer e infected with murine gamma-herpesvirus-68 (MHV-68), Atheroma formation wa s accelerated over a 24-week period in infected apoE-/- mice compared with control uninfected apoE-/- mice. Acceleration of atherosclerosis was reduce d by antiviral drug administration. Histological analysis of the atheromato us plaques showed no difference between lesions of infected and control mic e. Viral mRNA was present ill the aortas of infected mice before lesion dev elopment on day 5 after infection. This suggests that the virus may initiat e endothelial injury, which is believed to be an early event in the develop ment of atherosclerosis. Therefore, the virus may play a direct role in ath erosclerosis rather than be an "innocent bystander." Conclusions These data demonstrate that a gamma-herpesvirus can accelerate atherosclerosis in the apoE-/- mouse. This study provides the first report of a murine model in which to study the causative role of herpesvirus infec tion in the development of atherosclerosis.