(Circulation. 2000;102:779.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Herpesvirus Infection Accelerates Atherosclerosis in the Apolipoprotein E–Deficient Mouse
From the Wolfson Institute for Biomedical Research (D.G.A., K.L.P., D.A.G., C.G.-C.) and the Centre for Clinical Pharmacology and Therapeutics (D.G.A., P.V., C.G.-C.), University College London, London, UK.
Correspondence to Dr Dagmar G. Alber, Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6AU, UK. E-mail rmgzdga{at}ucl.ac.uk
Background—Human herpesviruses have been implicated but not proven to be involved 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 were infected with murine 
-herpesvirus-68 (MHV-68).
Atheroma formation was accelerated over a 24-week period in
infected apoE-/- mice compared with control uninfected apoE-/-
mice. Acceleration of atherosclerosis was reduced by
antiviral drug administration. Histological
analysis of the atheromatous plaques showed no
difference between lesions of infected and control mice. Viral mRNA was
present in the aortas of infected mice before lesion development on
day 5 after infection. This suggests that the virus may initiate
endothelial injury, which is believed to be an early
event in the development of atherosclerosis. Therefore,
the virus may play a direct role in atherosclerosis
rather than be an "innocent bystander."
Conclusions—These data demonstrate that a -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 infection in the development of
atherosclerosis.
Key Words: infection • atherosclerosis • viruses • apolipoproteins • pathology
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