Format

Send to

Choose Destination
EBioMedicine. 2016 Jul;9:195-206. doi: 10.1016/j.ebiom.2016.06.015. Epub 2016 Jun 11.

Regulation of Retinoic Acid Inducible Gene-I (RIG-I) Activation by the Histone Deacetylase 6.

Author information

1
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, 750 Republican St, Seattle, WA, USA; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, No. 1, Changde St, Taipei City, Taiwan. Electronic address: mliu@ntu.edu.tw.
2
Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, USA.
3
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, 750 Republican St, Seattle, WA, USA.
4
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, No. 1, Changde St, Taipei City, Taiwan.
5
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, 750 Republican St, Seattle, WA, USA. Electronic address: mgale@uw.edu.

Abstract

Retinoic acid inducible gene-I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the immune response against many RNA viruses. Upon RNA ligand binding, RIG-I undergoes a conformational change facilitating its homo-oligomerization and activation that results in its translocation from the cytosol to intracellular membranes to bind its signaling adaptor protein, mitochondrial antiviral-signaling protein (MAVS). Here we show that RIG-I activation is regulated by reversible acetylation. Acetyl-mimetic mutants of RIG-I do not form virus-induced homo-oligomers, revealing that acetyl-lysine residues of the RIG-I repressor domain prevent assembly to active homo-oligomers. During acute infection, deacetylation of RIG-I promotes its oligomerization upon ligand binding. We identify histone deacetylase 6 (HDAC6) as the deacetylase that promotes RIG-I activation and innate antiviral immunity to recognize and restrict RNA virus infection.

KEYWORDS:

Deacetylation; HCV; HDAC6; Innate immunity; Interferon; RIG-I; West Nile virus

PMID:
27372014
PMCID:
PMC4972567
DOI:
10.1016/j.ebiom.2016.06.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center