MicroRNAs regulate the immunometabolic response to viral infection in the liver

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1038/nchembio.1940
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Name affiliation
  1. National Research Council of Canada. Medical Devices
  2. National Research Council of Canada. Human Resources Branch
  3. National Research Council of Canada
FormatText, Article
Journal titleNature Chemical Biology
ISSN1552-4450
Volume11
Issue12
Pages988–993
Subject25 hydroxycholesterol; microRNA; microRNA 130B; microRNA 185; unclassified drug; animal experiment; animal model; antiviral activity; dendritic cell; gene expression; gene expression regulation; gene identification; gene repression; hepatitis C; Hepatitis C virus; human cell; human tissue; immunoregulation; lipid metabolism; lipid storage; liver metabolism; macrophage; metabolic regulation; microenvironment; mouse; virus immunity
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.
Publication date
PublisherNature Publishing Group
LanguageEnglish
Peer reviewedYes
NPARC number21277385
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Record created2016-03-09
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