on March 21, 2002
Published online before print March 21, 2002, doi: 10.1161/01.ATV.0000016046.94521.68
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Submitted on February 5, 2002
Accepted on February 27, 2002
Enhanced Atherogenesis Is Not an Obligatory
Response to Systemic Herpesvirus Infection in the ApoE-Deficient
Mouse. Comparison of Murine 
-Herpesvirus-68 and
Herpes Simplex Virus-1
Dagmar G. Alber *;
From the Wolfson Institute for Biomedical Research (D.G.A., K.L.P.) and the Centre for Clinical Pharmacology and Therapeutics (D.G.A., P.V.), Rayne Institute (BHF Laboratories), University College London, London, UK.
* To whom correspondence should be addressed. E-mail: d.alber{at}ucl.ac.uk.
Abstract—Viral
and bacterial infectious agents have been implicated in the etiology of
atherosclerosis. We have previously shown that a
-herpesvirus can accelerate atherosclerosis in the
apolipoprotein E--deficient (apoE-/-) mouse. To address whether a
virally induced systemic immune response is sufficient to trigger
enhanced atheroma formation, we infected apoE-/- mice
with murine -herpesvirus-68 (MHV-68) or herpes simplex virus-1
(HSV-1). In this study, we show that both viruses were able to induce a
cell-mediated and humoral immune response in the apoE-/- mouse,
which was sustained over a period of 24 weeks. Although intranasal or
intraperitoneal infection with MHV-68 induced
similar levels of virus-specific IgG1 and IgG2a antibodies in the serum
of apoE-/- mice, those infected with HSV-1 showed higher
anti--HSV-1 IgG2a compared with IgG1 antibody levels. In addition,
viral message was not detected in the aortas of HSV-1--infected
animals, whereas we have shown previously that MHV-68 mRNA can be
detected in the aortas of infected mice as early as 5 days after
infection. Compared with control mice, apoE-/- mice infected with
MHV-68 showed accelerated atherosclerosis, whereas mice
infected with HSV-1 did not. These data indicate that a systemic immune
response to any particular infectious agent is insufficient to induce
enhanced atherosclerosis in the apoE-/- mouse and
point to specific infections or immune mechanisms that might be
essential for virally enhanced
atherogenesis.
Key words: atherosclerosis • infection • herpesvirus • animal models