Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse.
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.


RESULTS
In the present study, 3- to 4-week-old apoE-/- mice were infected with murine gamma-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 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 infection in the development of atherosclerosis.
Alber
D G
DG
Wolfson Institute for Biomedical Research, University College London, London, UK. rmgzdga@ucl.ac.uk
Powell
K L
KL
Vallance
P
P
Goodwin
D A
DA
Grahame-Clarke
C
C
D000818:Animals; D000917:Antibody Formation; D000998:Antiviral Agents / Q000627:therapeutic use; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000473:pathology* / Q000821:virology*; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006564:Herpesviridae / Q000235:genetics / Q000302:isolation & purification; D006566:Herpesviridae Infections / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D013997:Time Factors
D000998:Antiviral Agents; D001057:Apolipoproteins E; D012333:RNA, Messenger; D012367:RNA, Viral; D002784:Cholesterol