Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3

• Main Authors: Chenyang Yi, Zongzheng Zhao, Shengyu Wang, Xin Sun, Dan Zhang, Xiaomei Sun, Anding Zhang, Meilin Jin
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-09-01
• Series: Frontiers in Immunology
• Subjects: polymerase; pdm/09; innate immunity; signaling pathway; phosphorylation
• Online Access: http://journal.frontiersin.org/article/10.3389/fimmu.2017.01051/full

The influenza A virus (IAV) can be recognized by retinoic acid-inducible gene I (RIG-I) to activate the type I interferon response and induce antiviral effects. The virus has evolved several strategies to evade the innate immune response, including non-structural protein 1 (NS1) and its polymerase subunits. The mechanism by which NS1 inhibits interferon-β (IFN-β) is well understood, whereas the mechanism by which polymerase acid protein (PA) inhibits IFN-β remains to be elucidated. In this study, we observed that the IAV PA protein could inhibit the production of IFN-β and interferon-stimulated genes induced by Sendai virus through interferon regulatory factor 3 (IRF3), but not through nuclear factor-kappaB (NF-kappaB). In addition, PA inhibited IFN-β induction by RIG-I, melanoma differentiation-associated gene 5, mitochondria antiviral signaling protein, TANK-binding kinase 1, inhibitor of nuclear factor kappa-B kinase-ε (IKKε), and IRF3 overexpression. Furthermore, PA interacted with IRF3 to block its activation. The N-terminal endonuclease activity of PA was responsible for its interaction with IRF3 and inhibition of the IFN-β signaling pathway. In summary, our data reveal the mechanism by which IAV PA inhibits the IFN-β signaling pathway, providing a new mechanism by which the virus antagonizes the antiviral signaling pathway.