| Literature DB >> 26479438 |
Ragunath Singaravelu1,2, Shifawn O'Hara2, Daniel M Jones3, Ran Chen4, Nathan G Taylor3, Prashanth Srinivasan1,2, Curtis Quan1,2, Dominic G Roy5, Rineke H Steenbergen4, Anil Kumar6, Rodney K Lyn2,7, Dennis Özcelik2,7, Yanouchka Rouleau2, My-Anh Nguyen1,8, Katey J Rayner1,8, Tom C Hobman6, David Lorne Tyrrell4, Rodney S Russell3, John Paul Pezacki1,2,7.
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.Entities:
Mesh：
Substances：
Year: 2015 PMID： 26479438 DOI： 10.1038/nchembio.1940
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040