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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:793.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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; Patrick Vallance^*; Kenneth L. Powell^*

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.

Correspondence to Dr Dagmar G. Alber, Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6BT, UK. E-mail d.alber{at}ucl.ac.uk

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

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