Picornavirus VP2 protein suppresses innate immunity through selective autophagic degradation of IKBKE/IKKε

Kangli Li1,2, Xiangle Zhang1,2, Dandan Dong1,2

  • 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, China.

Autophagy
|November 30, 2025
PubMed

Insights

Senecavirus A protein VP2 suppresses innate immunity by degrading IKBKE/IKKε via the RNF114-CALCOCO2 pathway. This conserved picornavirus mechanism aids immune evasion and informs oncolytic virus and vaccine development.

Area of Science:

  • Virology
  • Immunology
  • Oncolytic Virotherapy

Background:

  • Senecavirus A (SVA) is a picornavirus with potential for oncolytic virotherapy.
  • Understanding SVA's immune suppression is crucial for optimizing its therapeutic use.

Purpose of the Study:

  • To identify the viral immune suppressive factors of SVA.
  • To elucidate the mechanism by which SVA suppresses host innate immunity.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Western blotting and RT-PCR to assess protein degradation and gene expression.
  • siRNA-mediated knockdown to investigate the roles of specific proteins.

Main Results:

  • SVA structural protein VP2 was identified as a key immune suppressive factor.
  • VP2 targets IKBKE/IKKε for degradation through interaction with CALCOCO2/NDP52 and promotion of RNF114-mediated ubiquitination.
  • This VP2-RNF114-IKBKE/IKKε-CALCOCO2 axis suppresses host innate immune responses.
  • The mechanism is conserved among picornaviruses.

Conclusions:

  • SVA VP2 employs a novel immune evasion strategy by degrading IKBKE/IKKε.
  • This mechanism is conserved across picornaviruses, highlighting a common immune suppression pathway.
  • Findings provide insights for developing SVA-based oncolytic viruses, vaccines, and antiviral therapies.

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