摘要
Recognition of viral dsRNA by Toll-like receptor 3(TLR3)leads to the induction of downstream antiviral effectors and the innate antiviral immune response.Here,we identified the zinc-finger FYVE domain-containing protein ZFYVE1,a guanylate-binding protein(GBP),as a positive regulator of TLR3-mediated signaling.Overexpression of ZFYVE1 promoted the transcription of downstream antiviral genes upon stimulation with the synthetic TLR3 ligand poly(I:C).Conversely,ZFYVE1 deficiency had the opposite effect.Zfyve1^(−/−) mice were less susceptible than wild-type mice to inflammatory death induced by poly(I:C)but not LPS.ZFYVE1 was associated with TLR3,and the FYVE domain of ZFYVE1 and the ectodomain of TLR3 were shown to be responsible for their interaction.ZFYVE1 was bound to poly(I:C)and increased the binding affinity of TLR3 to poly(I:C).These findings suggest that ZFYVE1 plays an important role in the TLR3-mediated innate immune and inflammatory responses by promoting the ligand binding of TLR3.
基金
This work was supported by grants from the State Key R&D Program of China(2017YFA0505800,2016YFA0502102 and 2018YFA0800700)
the National Natural Science Foundation of China(31830024,31630045,31870870,31800728,31771555,and 31671418)
the China Postdoctoral Science Foundation(2017M620334)
the Fundamental Research Funds for the Central Universities(2042019kf0204)
the Natural Science Foundation of Hubei Province(2018CFA016).