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Open Access Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E

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Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes. Therefore, we investigated whether MNV4 likewise altered atherosclerosis in ApoE –/– mice. In the presence of oxidized LDL, MNV4 infection of ApoE –/– bone marrow-derived macrophages increased the gene expression of the inflammatory markers inducible nitric oxide synthase, monocyte chemoattractant protein 1, and IL6. In addition, proteins involved in cholesterol transport were altered in MNV4-infected ApoE –/– bone marrow-derived macrophages and consisted of increased CD36 and decreased ATP-binding cassette transporter A1. MNV4 infection of ApoE –/– mice at 12 wk of age (during the development of atherosclerosis) had a variable effect on atherosclerotic lesion size. In one study, MNV4 significantly increased atherosclerotic plaque area whereas in a second study, no effect was observed. Compared with controls, MNV4-infected mice had higher circulating Ly6C-positive monocytes, and viral RNA was detected in the aortas of some mice, suggesting potential mechanisms by which MNV4 alters disease progression. Plaque size did not differ when ApoE –/– mice were infected at 4 wk of age (early during disease development) or in ApoE –/– mice maintained on a high-fat, high-cholesterol diet. Therefore, these data show that MNV4 has the potential to exert a variable and unpredictable effect on atherosclerosis in ApoE –/– mice. We therefore propose that performing experiments in MNV-free mouse colonies is warranted.

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Document Type: Research Article

Affiliations: 1: Department of Comparative Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA. [email protected] 2: Department of Comparative Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA 3: Department of Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA 4: Department of Pathology, Department of Medicine, University of Washington, Seattle, Washington, USA

Publication date: October 1, 2015

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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