A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity

作者：Chan Ying Kai; Gack Michaela U^*

来源：Nature Immunology, 2016, 17(5): 523-+.

DOI：10.1038/ni.3393

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.

• 出版日期2016-5