title: Retinoid X receptor α attenuates host antiviral response by suppressing type I interferon.
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.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Su-Yang
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Bahram
authors.initials: B
authors.lastname: Razani
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Arora
authors.affiliation: Department of Biological Chemistry, University of California, Los Angeles, California 90095, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.affiliation: Cardiovascular Development and Repair Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Núñez
authors.affiliation: Cardiovascular Development and Repair Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ricote
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D057809:HEK293 Cells; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D008024:Ligands; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011070:Poly I-C / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D047490:Retinoid X Receptor alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D054243:Vesicular Stomatitis / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D010948:Viral Plaque Assay; D051176:beta Catenin / Q000378:metabolism
chemical_list: C430898:AGN 194204; D005231:Fatty Acids, Unsaturated; D008024:Ligands; D034741:RNA, Small Interfering; D047490:Retinoid X Receptor alpha; D013764:Tetrahydronaphthalenes; D051176:beta Catenin; D016899:Interferon-beta; D011070:Poly I-C