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Foot-and-mouth disease virus 3D polymerase antagonizes the interferon signaling pathway by blocking STAT2 nuclear

Kangli Li1, Boning Zhu1, Shuo Wang2

  • 1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; WOAH/National reference laboratory for foot-and-mouth disease, Lanzhou 730046, China.

Virus Research
|December 3, 2025
PubMed

Insights

Foot-and-mouth disease virus (FMDV) 3D polymerase inhibits the JAK-STAT pathway by targeting STAT2. This discovery reveals a new FMDV immune evasion strategy, crucial for developing antiviral treatments.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Foot-and-mouth disease virus (FMDV) causes highly contagious and destructive disease in cloven-hoofed animals.
  • FMDV is known to suppress innate immunity, with research focusing on 3C and L proteinases.
  • The role of FMDV 3D polymerase in inhibiting the interferon (IFN) signaling pathway is not well understood.

Purpose of the Study:

  • To investigate the role of FMDV 3D polymerase in the inhibition of the host innate immune response.
  • To elucidate the mechanism by which FMDV 3D polymerase interferes with the IFN signaling pathway.

Main Methods:

  • Investigated the effect of FMDV 3D polymerase on the JAK-STAT signaling pathway.
  • Assessed the interaction between FMDV 3D polymerase and STAT2.
  • Analyzed the impact of 3D polymerase on STAT2 phosphorylation and nuclear translocation.
  • Evaluated the activity of the interferon-stimulated response element (ISRE) promoter.

Main Results:

  • FMDV 3D polymerase was found to inhibit the activation of the JAK-STAT signaling pathway.
  • The study demonstrated that 3D polymerase targets STAT2, hindering its phosphorylation and nuclear translocation.
  • FMDV 3D polymerase significantly inhibited ISRE promoter activity and downregulated interferon-stimulated genes.
  • A novel mechanism of FMDV immune evasion involving 3D polymerase and STAT2 was identified.

Conclusions:

  • FMDV 3D polymerase acts as an inhibitor of the JAK-STAT signaling pathway by targeting STAT2.
  • This interaction suppresses IFN signaling and antagonizes the host antiviral immune response.
  • Findings provide crucial insights for developing novel anti-FMDV strategies.
Keywords:
3D proteinFMDVInnate immune responseNuclear translocationSTAT2

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