FKBP5 Regulates RIG-I-Mediated NF-κB Activation and Influenza A Virus Infection

Viruses. 2020 Jun 22;12(6):672. doi: 10.3390/v12060672.

Abstract

Influenza A virus (IAV) is a highly transmissible respiratory pathogen and is a constant threat to global health with considerable economic and social impact. Influenza viral RNA is sensed by host pattern recognition receptors (PRRs), such as the Toll-like receptor 7 (TLR7) and retinoic acid-inducible gene I (RIG-I). The activation of these PRRs instigates the interferon regulatory factor (IRF) and nuclear factor kappa B (NF-κB) signaling pathways that induce the expression of interferon-stimulated genes (ISGs) and inflammatory genes. FK506-binding protein 5 (FKBP5) has been implied in the IκBα kinase (IKK) complex. However, the role of FKBP5 in the RIG-I signaling and IAV infection is not well elucidated. Here, we demonstrate that the knockout of FKBP5 increases IAV infection. Furthermore, FKBP5 binds IKKα, which is critical for RIG-I-induced innate immune responses and ISG expression. Taken together, FKBP5 is a novel anti-influenza host factor that restricts IAV infection by the activation of RIG-I-mediated NF-κB signaling.

Keywords: IKK; antiviral; flu; host defense; immunophilin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A549 Cells
  • CRISPR-Cas Systems / genetics
  • Cell Line
  • DEAD Box Protein 58 / metabolism*
  • Gene Knockout Techniques
  • HEK293 Cells
  • Humans
  • Immunity, Innate / immunology
  • Influenza A virus / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / pathology
  • NF-KappaB Inhibitor alpha / metabolism*
  • NF-kappa B / metabolism
  • Receptors, Immunologic
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism*

Substances

  • NF-kappa B
  • Receptors, Immunologic
  • NF-KappaB Inhibitor alpha
  • RIGI protein, human
  • DEAD Box Protein 58
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5