PMID- 26479438
OWN - NLM
STAT- MEDLINE
DCOM- 20160412
LR  - 20181113
IS  - 1552-4469 (Electronic)
IS  - 1552-4450 (Linking)
VI  - 11
IP  - 12
DP  - 2015 Dec
TI  - MicroRNAs regulate the immunometabolic response to viral infection in the liver.
PG  - 988-93
LID - 10.1038/nchembio.1940 [doi]
AB  - 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.
FAU - Singaravelu, Ragunath
AU  - Singaravelu R
AUID- ORCID: 0000-0002-2692-3650
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
FAU - O'Hara, Shifawn
AU  - O'Hara S
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
FAU - Jones, Daniel M
AU  - Jones DM
AD  - Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of 
      Newfoundland, St. John's, Newfoundland, Canada.
FAU - Chen, Ran
AU  - Chen R
AD  - 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.
FAU - Taylor, Nathan G
AU  - Taylor NG
AD  - Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of 
      Newfoundland, St. John's, Newfoundland, Canada.
FAU - Srinivasan, Prashanth
AU  - Srinivasan P
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
FAU - Quan, Curtis
AU  - Quan C
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
FAU - Roy, Dominic G
AU  - Roy DG
AD  - Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, 
      Ottawa, Ontario, Canada.
FAU - Steenbergen, Rineke H
AU  - Steenbergen RH
AD  - 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.
FAU - Kumar, Anil
AU  - Kumar A
AD  - Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
FAU - Lyn, Rodney K
AU  - Lyn RK
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
AD  - Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, 
      Ontario, Canada.
FAU - Ozcelik, Dennis
AU  - Ozcelik D
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
AD  - Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, 
      Ontario, Canada.
FAU - Rouleau, Yanouchka
AU  - Rouleau Y
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
FAU - Nguyen, My-Anh
AU  - Nguyen MA
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
FAU - Rayner, Katey J
AU  - Rayner KJ
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
FAU - Hobman, Tom C
AU  - Hobman TC
AD  - Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
FAU - Tyrrell, David Lorne
AU  - Tyrrell DL
AD  - 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.
FAU - Russell, Rodney S
AU  - Russell RS
AUID- ORCID: 0000-0002-0051-746X
AD  - Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of 
      Newfoundland, St. John's, Newfoundland, Canada.
FAU - Pezacki, John Paul
AU  - Pezacki JP
AD  - Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 
      Ottawa, Ontario, Canada.
AD  - Life Sciences Division, National Research Council of Canada, Ottawa, Ontario, 
      Canada.
AD  - Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, 
      Ontario, Canada.
LA  - eng
GR  - 136807/Canadian Institutes of Health Research/Canada
GR  - 232063/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151019
PL  - United States
TA  - Nat Chem Biol
JT  - Nature chemical biology
JID - 101231976
RN  - 0 (Antiviral Agents)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (MicroRNAs)
RN  - 767JTD2N31 (25-hydroxycholesterol)
SB  - IM
CIN - Nat Chem Biol. 2015 Dec;11(12):905-6. PMID: 26575235
MH  - Antiviral Agents/metabolism/pharmacology
MH  - Cell Line
MH  - Hepacivirus/drug effects
MH  - Hepatitis C/drug therapy/*immunology/*metabolism
MH  - Humans
MH  - Hydroxycholesterols/pharmacology
MH  - Liver/drug effects/*immunology/*metabolism/virology
MH  - MicroRNAs/genetics/*metabolism
MH  - Molecular Conformation
EDAT- 2015/10/20 06:00
MHDA- 2016/04/14 06:00
CRDT- 2015/10/20 06:00
PHST- 2015/03/04 00:00 [received]
PHST- 2015/09/11 00:00 [accepted]
PHST- 2015/10/20 06:00 [entrez]
PHST- 2015/10/20 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
AID - nchembio.1940 [pii]
AID - 10.1038/nchembio.1940 [doi]
PST - ppublish
SO  - Nat Chem Biol. 2015 Dec;11(12):988-93. doi: 10.1038/nchembio.1940. Epub 2015 Oct 
      19.