dc.contributor.author | Chan, Ying Kai | en_US |
dc.contributor.author | Gack, Michaela U. | en_US |
dc.date.accessioned | 2016-11-18T20:05:08Z | |
dc.date.issued | 2016 | en_US |
dc.identifier.citation | Chan, Ying Kai, and Michaela U. Gack. 2016. “A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity.” Nature immunology 17 (5): 523-530. doi:10.1038/ni.3393. http://dx.doi.org/10.1038/ni.3393. | en |
dc.identifier.issn | 1529-2908 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407587 | |
dc.description.abstract | 14-3-3 proteins regulate biological processes by binding to phospho-Ser or phospho-Thr motifs of cellular proteins. Among them, 14-3-3ε is crucial for antiviral immunity by mediating the cytosol-to-mitochondrial-membrane translocation of the pathogen sensor RIG-I. Here we show that the NS3 protein of dengue virus (DV) binds to 14-3-3ε and prevents RIG-I translocation to the adaptor MAVS, thereby blocking antiviral signaling. Intriguingly, a highly conserved phosphomimetic RxEP motif in NS3 is essential for 14-3-3ε binding. A recombinant mutant DV deficient in 14-3-3ε binding is impaired in RIG-I antagonism and elicits 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 may guide the rational design of therapeutics. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/ni.3393 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837045/pdf/ | en |
dash.license | LAA | en_US |
dc.title | A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nature immunology | en |
dc.date.available | 2016-11-18T20:05:08Z | |
dc.identifier.doi | 10.1038/ni.3393 | * |