title: MicroRNAs regulate the immunometabolic response to viral infection in the liver.
abstract: 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.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Ragunath
authors.identifier: http://orcid.org/0000-0002-2692-3650
authors.initials: R
authors.lastname: Singaravelu
authors.affiliation: Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Shifawn
authors.initials: S
authors.lastname: O'Hara
authors.affiliation: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Jones
authors.affiliation: 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.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Taylor
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Quan
authors.affiliation: Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Dominic G
authors.initials: DG
authors.lastname: Roy
authors.affiliation: 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.
authors.forename: Rineke H
authors.initials: RH
authors.lastname: Steenbergen
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.|Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Rodney K
authors.initials: RK
authors.lastname: Lyn
authors.affiliation: Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.|Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dennis
authors.initials: D
authors.lastname: Özcelik
authors.affiliation: Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Yanouchka
authors.initials: Y
authors.lastname: Rouleau
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: My-Anh
authors.initials: MA
authors.lastname: Nguyen
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Katey J
authors.initials: KJ
authors.lastname: Rayner
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Tom C
authors.initials: TC
authors.lastname: Hobman
authors.affiliation: 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.
authors.forename: David Lorne
authors.initials: DL
authors.lastname: Tyrrell
authors.affiliation: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Rodney S
authors.identifier: http://orcid.org/0000-0002-0051-746X
authors.initials: RS
authors.lastname: Russell
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.|Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, Canada.|Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Pezacki
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008968:Molecular Conformation
chemical_list: D000998:Antiviral Agents; D006888:Hydroxycholesterols; D035683:MicroRNAs; C007997:25-hydroxycholesterol