Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response.
RIG-I is an intracellular RNA virus sensor that mediates a signaling pathway that triggers the alpha/beta interferon (IFN-α/β) immune defenses. However, the mechanism for regulation of RIG-I activity remains largely unknown. Here we show that RIG-I activity is regulated by phosphorylation and dephosphorylation in its repressor domain (RD). Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of RIG-I are phosphorylated by casein kinase II (CK2) in the resting state of the cell and dephosphorylated when cells are infected by RNA virus. Mutation at aa position 770 or 854 to 855 of RIG-I renders it constitutively active. Pharmacological inhibition of CK2 enhances virus-induced expression of IFN-β and suppresses virus proliferation, while inhibition of phosphatase reduces virus-induced expression of IFN-β. Overexpression of CK2 suppresses RIG-I-mediated signaling, while silencing of CK2 results in the increased suppression of virus proliferation. Our results reveal a novel mechanism of the regulation of RIG-I activity during RNA virus infection.
National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871, China.
Zhiguo
Z
Sun
Hongwei
H
Ren
Yan
Y
Liu
Jessica L
JL
Teeling
Jun
J
Gu
D019943:Amino Acid Substitution / Q000235:genetics; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011971:Receptors, Immunologic; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014780:Viruses / Q000276:immunology*
D016898:Interferon-alpha; D011971:Receptors, Immunologic; D013912:Threonine; D012694:Serine; D016899:Interferon-beta; D047390:Casein Kinase II; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases