MicroRNAs regulate the immunometabolic response to viral infection in the liver

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

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Cell Line
  • Hepacivirus / drug effects
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology*
  • Hepatitis C / metabolism*
  • Humans
  • Hydroxycholesterols / pharmacology
  • Liver / drug effects
  • Liver / immunology*
  • Liver / metabolism*
  • Liver / virology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Conformation

Substances

  • Antiviral Agents
  • Hydroxycholesterols
  • MicroRNAs
  • 25-hydroxycholesterol