2. Academic Validation
  3. Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon

Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon

  • Nat Commun. 2014 Nov 24;5:5494. doi: 10.1038/ncomms6494.
Feng Ma 1,  Su-Yang Liu 1,  Bahram Razani 1,  Neda Arora 1,  Bing Li 2,  Hiroyuki Kagechika 3,  Peter Tontonoz 4,  Vanessa Núñez 5,  Mercedes Ricote 5,  Genhong Cheng 1
Affiliations

Affiliations

  • 1 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
  • 2 Department of Biological Chemistry, University of California, Los Angeles, California 90095, USA.
  • 3 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
  • 4 1] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA [2] Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA.
  • 5 Cardiovascular Development and Repair Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
PMID: 25417649 DOI: 10.1038/ncomms6494
Abstract

The retinoid X receptor α (RXRα), a key nuclear receptor in metabolic processes, is downregulated during host Antiviral response. However, the roles of RXRα in host Antiviral response are unknown. Here we show that RXRα overexpression or ligand activation increases host susceptibility to viral infections in vitro and in vivo, while Rxra-/- or antagonist treatment reduces Infection by the same viruses. Consistent with these functional studies, ligand activation of RXR inhibits the expression of Antiviral genes including type I interferon (IFN) and Rxra-/- macrophages produce more IFNβ than WT macrophages in response to polyI:C stimulation. Further results indicate that ligand activation of RXR suppresses the nuclear translocation of β-catenin, a co-activator of IFNβ enhanceosome. Thus, our studies have uncovered a novel RXR-dependent innate immune regulatory pathway, suggesting that the downregulation of RXR expression or RXR antagonist treatment benefits host Antiviral response, whereas RXR agonist treatment may increase the risk of viral infections.

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