期刊
NATURE IMMUNOLOGY
卷 17, 期 5, 页码 523-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3393
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资金
- US National Institutes of Health [R01 AI087846]
- Giovanni Armenise-Harvard Foundation
- William F. Milton Fund
- John and Virginia Kaneb Fellowship
14-3-3 proteins regulate biological processes by binding to phosphorylated serine or phosphorylated threonine motifs of cellular proteins. Among the 14-3-3 proteins, 14-3-3 epsilon serves a crucial function in antiviral immunity by mediating the cytosol-to-mitochondrial membrane translocation of the pathogen sensor RIG-I. Here we found that the NS3 protein of dengue virus (DV) bound to 14-3-3 epsilon and prevented translocation of RIG-I to the adaptor MAVS and thereby blocked antiviral signaling. Intriguingly, a highly conserved phosphomimetic RxEP motif in NS3 was essential for the binding of 14-3-3 epsilon. A recombinant mutant DV deficient in binding to 14-3-3 epsilon showed impairment in antagonism of RIG-I and elicited a markedly augmented innate immune response and enhanced T cell activation. Our work reveals a novel phosphomimetic-based mechanism for viral antagonism of 14-3-3-mediated immunity, which might guide the rational design of therapeutics.
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