@article{Receptor-Based:2561,
      recid = {2561},
      author = {Riedl, William},
      title = {Flaviviral Antagonism of RIG-I-like Receptor-Based  Immunity},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2020-08},
      pages = {119},
      abstract = {Mosquito-transmitted flaviviruses, including the recently  emergent Zika virus (ZIKV), represent a major human health  concern. Detection of viral infection by cellular pattern  recognition receptors (PRRs) is a critical first step in  generating a type-I interferon (IFN) mediated antiviral  program. RIG-I and MDA5, the PRRs responsible for detecting  cytosolic RNA, bind to viral nucleic acid and initiate  downstream signaling by interacting with the downstream  adaptor protein MAVS. Translocation of these sensors from  the cytosolic site of RNA detection to the mitochondria is  mediated by binding to cellular 14-3-3 chaperone proteins.  ZIKV NS3 encodes a phosphomimetic 14-3-3-binding motif  (64-RLDP-67) that mediates an interaction between NS3 and  14-3-3 proteins. In the context of viral infection,  mutational perturbation of the 14-3-3 interaction site in  NS3 spurs an enhanced production of cytokines and impairs  ZIKV infection. Our results demonstrate that ZIKV NS3  evades RIGI- and MDA5-mediated innate immunity through an  NS3-14-3-3 protein interaction, and loss of this evasion  ability attenuates viral replication. Furthermore, an  ability to bind to 14-3-3 proteins is conserved in other  members of Flaviviridae.},
      url = {http://knowledge.uchicago.edu/record/2561},
      doi = {https://doi.org/10.6082/uchicago.2561},
}