The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon
- 1 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Microbiology
- Vol. 5 (1), 84-+
- https://doi.org/10.1038/s41564-019-0602-7
Abstract
Evidence has accumulated to demonstrate that the intestinal microbiota enhances mammalian enteric virus infections(1). For example, we and others previously reported that commensal bacteria stimulate acute and persistent murine norovirus infections(2-4). However, in apparent contradiction of these results, the virulence of murine norovirus infection was unaffected by antibiotic treatment. This prompted us to perform a detailed investigation of murine norovirus infection in microbially deplete mice, revealing a more complex picture in which commensal bacteria inhibit viral infection of the proximal small intestine while simultaneously stimulating the infection of distal regions of the gut. Thus, commensal bacteria can regulate viral regionalization along the intestinal tract. We further show that the mechanism underlying bacteria-dependent inhibition of norovirus infection in the proximal gut involves bile acid priming of type III interferon. Finally, the regional effects of the microbiota on norovirus infection may result from distinct regional expression profiles of key bile acid receptors that regulate the type III interferon response. Overall, these findings reveal that the biotransformation of host metabolites by the intestinal microbiota directly and regionally impacts infection by a pathogenic enteric virus.Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (T90DE021990, T90DE021990)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (T32DK094775)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R21AI103961, R01AI141478, K22AI127846, R01AI081921, R01AI141478, R01AI116892)
- UChicago | Digestive Diseases Reseach Core Center, University of Chicago (P30 DK052574)
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