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- Title
FKBP8 inhibits virus‐induced RLR‐VISA signaling.
- Authors
Xu, Shan‐Shan; Xu, Liang‐Guo; Yuan, Cailei; Li, Sheng‐Na; Chen, Tian; Wang, Weiying; Li, Changsheng; Cao, Lingzhen; Rao, Hua
- Abstract
The mitochondrial antiviral signal protein mitochondrial antiviral signaling protein, also known as virus‐induced signaling adaptor (VISA), plays a key role in regulating host innate immune signaling pathways. This study identifies FK506 binding protein 8 (FKBP8) as a candidate interacting protein of VISA through the yeast two‐hybrid technique. The interaction of FKBP8 with VISA, retinoic acid inducible protein 1 (RIG‐I), and IFN regulatory factor 3 (IRF3) was confirmed during viral infection in mammalian cells by coimmunoprecipitation. Overexpression of FKBP8 using a eukaryotic expression plasmid significantly attenuated Sendai virus–induced activation of the promoter interferons β (IFN‐β), and transcription factors nuclear factor κ‐light chain enhancer of activated B cells (NF‐κB) and IFN‐stimulated response element (ISRE). Overexpression of FKBP8 also decreased dimer‐IRF3 activity, but enhanced virus replication. Conversely, knockdown of FKBP8 expression by RNA interference showed opposite effects. Further studies indicated that FKBP8 acts as a negative interacting partner to regulate RLR‐VISA signaling by acting on VISA and TANK binding kinase 1 (TBK1). Additionally, FKBP8 played a negative role on virus‐induced signaling by inhibiting the formation of TBK1‐IRF3 and VISA‐TRAF3 complexes. Notably, FKBP8 also promoted the degradation of TBK1, RIG‐I, and TRAF3 resulting from FKBP8 reinforced Sendai virus–induced endogenous polyubiquitination of RIG‐I, TBK1, and TNF receptor‐associated factor 3 (TRAF3). Therefore, a novel function of FKBP8 in innate immunity antiviral signaling regulation was revealed in this study. We revealed FKBP8 is an negatively regulator in innate immunity anti viral signaling regulation and FKBP8 is involved in the regulation of signaling pathway through interaction with other proteins.
- Publication
Journal of Medical Virology, 2019, Vol 91, Issue 3, p482
- ISSN
0146-6615
- Publication type
Article
- DOI
10.1002/jmv.25327