. 2022 Jul 20;574:47-56.
doi: 10.1016/j.virol.2022.07.002. Online ahead of print.
Influenza virus NS1 interacts with 14-3-3ε to antagonize the production of RIG-I-mediated type I interferons

Tong Wang 1 , Fanhua Wei 2 , Zhimin Jiang 1 , Jingwei Song 1 , Chengye Li 2 , Jinhua Liu 3



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.

Keywords: 14-3-3 proteins; Influenza virus; NS1 protein; RIG-I translocation.