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  • Title: Influenza virus NS1 interacts with 14-3-3ε to antagonize the production of RIG-I-mediated type I interferons.
    Author: Wang T, Wei F, Jiang Z, Song J, Li C, Liu J.
    Journal: Virology; 2022 Sep; 574():47-56. PubMed ID: 35926243.
    Abstract:
    For influenza A viruses (IAVs), non-structural protein 1 (NS1) protein was recognized to be the key factor to enhance virulence by antagonizing host innate anti-viral responses. However, for the pathways allowing NS1 to regulate the type I interferon (IFN) response, the identification of the substrates was still incomplete. Here a recombinant IAV encoding a NS1 containing an affinity tag (NS1-Strep) was generated to capture the NS1-interactome in the lungs of infected mice. Several scaffold proteins of the 14-3-3 family were distinguished as the most potent candidates. Based on the conserved motif RxxTxxT of NS1, the interaction between NS1 and 14-3-3ε was enabled, which competed for the binding of RIG-I to 14-3-3ε and prevented RIG-I translocation to the adaptor MAVS, consequently inhibiting IFN-β expression. A recombinant mutant IAV deficient in 14-3-3ε binding elicited a markable innate immune responses and showed impaired growth kinetics.
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