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Nat Chem Biol. 2015 Dec;11(12):988-93. doi: 10.1038/nchembio.1940. Epub 2015 Oct 19.

MicroRNAs regulate the immunometabolic response to viral infection in the liver.

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Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.
Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Department of Medical Microbiology and Immunology, University of Alberta and Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta, Canada.
Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.


Immune regulation of cellular metabolism can be responsible for successful responses to invading pathogens. Viruses alter their hosts' cellular metabolism to facilitate infection. Conversely, the innate antiviral responses of mammalian cells target these metabolic pathways to restrict viral propagation. We identified miR-130b and miR-185 as hepatic microRNAs (miRNAs) whose expression is stimulated by 25-hydroxycholesterol (25-HC), an antiviral oxysterol secreted by interferon-stimulated macrophages and dendritic cells, during hepatitis C virus (HCV) infection. However, 25-HC only directly stimulated miR-185 expression, whereas HCV regulated miR-130b expression. Independently, miR-130b and miR-185 inhibited HCV infection. In particular, miR-185 significantly restricted host metabolic pathways crucial to the HCV life cycle. Interestingly, HCV infection decreased miR-185 and miR-130b levels to promote lipid accumulation and counteract 25-HC's antiviral effect. Furthermore, miR-185 can inhibit other viruses through the regulation of immunometabolic pathways. These data establish these microRNAs as a key link between innate defenses and metabolism in the liver.

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