Type 1 Interferon

• Evidence that viruses evade this response

  • Several viruses have proteins capable of inhibiting essential binding processes in the pathway
  • Examples include the NS5 protein from the yellow fever virus, Vp40 protein from the Ebola virus, measles V protein, Zika Ns5 protein, NS5 protein of west nile and tick-borne encephalitis viruses
• Interferon got its name as it 'interferes' with virus production and replication
• Cytokines in the innate immune system

  • Primarily produced by infected cells
  • Act on neighboring cells by binding to interferon receptors
  • Comprised of 13 subtypes
• When the pathway is activated

  1. Type 1 IFN binds to the IFNAR1/IFNAR2 heterodimer receptor and signal transduction is initiated by pre-associated Janus tyrosine kinases (JAK1 and TYK2)

  2. Phosphorylation of the IFNAR1 chain leads to the recruitment of signal transducers and activators of transcription (STATs)

  3. Heterodimers between STAT1 and STAT2 associate with IFN regulatory factor 9 (IRF9), forming the IFN-stimulated transcription factor (ISGF3)

  4. ISGF3 translocates to the nucleus and binds to the ISRE promoter site, resulting in antiviral protection
• Interferons

  1. Classified according to the receptor complex they signal through

  2. Type I interferons bind to IFNAR
• IFN production is triggered by the detection of PAMPs/DAMPs by host cell sensors


  • Trigger: viral nucleic acid, e.g., dsRNA, ssRNA
  • Sensors: e.g., RIG-1, TLRs
• This contributes to antiviral immunity

  • Proteins transcribed as a result trigger key steps in the antiviral pathway
  • Proteins include ISG15, the GTPase Mx1, ribonuclease L (RNaseL) and protein kinase R (PKR)