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Murine Norovirus: An Intercurrent Variable in a Mouse Model of Bacteria-Induced Inflammatory Bowel Disease

Lencioni, Karen Chase and Seamons, Audrey and Treuting, Piper M. and Maggio-Price, Lillian and Brabb, Thea (2008) Murine Norovirus: An Intercurrent Variable in a Mouse Model of Bacteria-Induced Inflammatory Bowel Disease. Comparative Medicine, 58 (6). pp. 522-533. ISSN 1532-0820.

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Murine norovirus (MNV) has recently been recognized as a widely prevalent viral pathogen in mouse colonies and causes disease and mortality in mice with impaired innate immunity. We tested the hypothesis that MNV infection would alter disease course and immune responses in mice with inflammatory bowel disease (IBD). FVB.129P2-Abcb1a^(tm1Bor) N7 (Mdr1a−/−) mice develop spontaneous IBD that is accelerated by infection with Helicobacter bilis. As compared with controls, Mdr1a−/− mice coinfected with MNV4 and H. bilis showed greater weight loss and IBD scores indicative of severe colitis, demonstrating that MNV4 can modulate the progression of IBD. Compared with controls, mice inoculated with MNV4 alone had altered levels of serum biomarkers, and flow cytometric analysis of immune cells from MNV4-infected mice showed changes in both dendritic cell (CD11c+) and other nonT cell (CD4− CD8−) populations. Dendritic cells isolated from MNV4-infected mice induced higher IFNγ production by polyclonal T cells in vitro at 2 d after infection but not at later time points, indicating that MNV4 infection enhances antigen presentation by dendritic cells early after acute infection. These findings indicate that acute infection with MNV4 is immunomodulatory and alters disease progression in a mouse model of IBD.

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Additional Information:© 2008 American Association for Laboratory Animal Science. Received May 5, 2008; Revised June 10, 2008; Accepted August 1, 2008. Published online 2008 December. The studies described here were supported by the Department of Comparative Medicine, University of Washington. KLC was supported by training grant T-32 RR007019 from the National Institutes of Health. We thank Lela Riley (University of Missouri) for providing MNV4. We are grateful to Rolf Drivdahl, LapHin Lai, Aimee McMillan, Susan Phelps, and Tiffany Wakayama (University of Washington) for their technical assistance.
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University of Washington Department of Comparative MedicineUNSPECIFIED
NIHT-32 RR007019
Issue or Number:6
Record Number:CaltechAUTHORS:20101208-153402696
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:21250
Deposited By: Tony Diaz
Deposited On:14 Dec 2010 21:16
Last Modified:03 Oct 2019 02:21

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