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


ABSTRACT: The retinoid X receptor ? (RXR?), a key nuclear receptor in metabolic processes, is downregulated during host antiviral response. However, the roles of RXR? in host antiviral response are unknown. Here we show that RXR? 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 IFN? than WT macrophages in response to polyI:C stimulation. Further results indicate that ligand activation of RXR suppresses the nuclear translocation of ?-catenin, a co-activator of IFN? 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.

SUBMITTER: Ma F 

PROVIDER: S-EPMC4380327 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Ma Feng F   Liu Su-Yang SY   Razani Bahram B   Arora Neda N   Li Bing B   Kagechika Hiroyuki H   Tontonoz Peter P   Núñez Vanessa V   Ricote Mercedes M   Cheng Genhong G  

Nature communications 20141124


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 a  ...[more]

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