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

Lencioni, Karen C. and Drivdahl, Rolf and Seamons, Audrey and Treuting, Piper M. and Brabb, Thea and Maggio-Price, Lillian (2011) Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer. Comparative Medicine, 61 (3). pp. 219-226. ISSN 1532-0820.

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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.

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Additional Information:© 2011 American Association for Laboratory Animal Science. Received: 24 Nov 2010; Revision requested: 25 Dec 2010; Accepted: 17 Jan 2011. KLC was supported by training grant T-32 RR007019 from the NIH. We thank Lela Riley (University of Missouri) for providing the MNV4, and we are grateful to Aimee McMillan for animal colony and technical support.
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NIHT-32 RR007019
Subject Keywords:BMDM, bone-marrow–derived macrophages; IBD, inflammatory bowel disease; MNV, murine norovirus
Issue or Number:3
Record Number:CaltechAUTHORS:20120423-133751353
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30260
Deposited By: Jason Perez
Deposited On:24 Apr 2012 14:18
Last Modified:03 Oct 2019 03:48

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