title: Interferon regulatory factor 3 is a key regulation factor for inducing the expression of SAMHD1 in antiviral innate immunity.
abstract: SAMHD1 is a type I interferon (IFN) inducible host innate immunity restriction factor that inhibits an early step of the viral life cycle. The underlying mechanisms of SAMHD1 transcriptional regulation remains elusive. Here, we report that inducing SAMHD1 upregulation is part of an early intrinsic immune response via TLR3 and RIG-I/MDA5 agonists that ultimately induce the nuclear translocation of the interferon regulation factor 3 (IRF3) protein. Further studies show that IRF3 plays a major role in upregulating endogenous SAMHD1 expression in a mechanism that is independent of the classical IFN-induced JAK-STAT pathway. Both overexpression and activation of IRF3 enhanced the SAMHD1 promoter luciferase activity, and activated IRF3 was necessary for upregulating SAMHD1 expression in a type I IFN cascade. We also show that the SAMHD1 promoter is a direct target of IRF3 and an IRF3 binding site is sufficient to render this promoter responsive to stimulation. Collectively, these findings indicate that upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3 and we suggest that type I IFN induction and induced SAMHD1 expression are coordinated.
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Shen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Xuchen
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Lingxue
authors.initials: L
authors.lastname: Yu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Wu
authors.initials: W
authors.lastname: Tong
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Qinfeng
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Tong
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D000076106:SAM Domain and HD Domain-Containing Protein 1 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013552:Swine; D015854:Up-Regulation / Q000235:genetics
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human