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Open Access Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer

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Murine norovirus (MNV) is endemic in mouse research facilities in the United States and Europe, with a prevalence as high as 58% to 64%. Because of MNV's orofecal route of infection, clinically silent persistent infections in some mouse strains, and proclivity for macrophage and dendritic cells, its presence in mouse colonies has potential to alter phenotypes in experimental mouse models, particularly those involving inflammation and immunologic responses. Although MNV is subclinical, not causing overt disease in immunocompetent mice, we found that MNV infection can accelerate bacteria–induced inflammatory bowel disease (IBD) progression in Mdr1a–/– mice. The studies presented here examined whether MNV infection also affects the phenotype of a bacterially driven mouse model of inflammation–associated colon cancer in genetically susceptible Smad3–/– mice. In vitro culture of bone–marrow—derived macrophages (BMDM) was used to determine whether MNV4 influenced macrophage cytokine production. For in vivo studies, Smad3–/– mice were infected with MNV4 one week prior to infection with Helicobacter. Mice were monitored for 17 to 32 wk for development of IBD and colon cancer, and tissues were analyzed histopathologically. Although in vitro infection of BMDM with MNV4 led to increased inflammatory cytokine production, infection with MNV4 in vivo did not result in any statistically significant differences in survival, IBD scores, tumor incidence, or tumor phenotype in Smad3–/– mice. In addition, MNV infection alone did not result in IBD or colon cancer. Therefore MNV infection alone or in conjunction with Helicobacter does not alter the development or progression of IBD or colon cancer in Smad3–/– mice.

Document Type: Research Article

Affiliations: 1: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA; Office of Laboratory Resources, California Institute of Technology, Pasadena, California, USA 2: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA 3: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.

Publication date: 2011-06-01

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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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