Foot‐and‐mouth disease virus evades innate immune response by 3c‐targeting of mda5

Hyejin Kim, Ah Young Kim, Jieun Choi, Sun Young Park, Sang Hyun Park, Jae Seok Kim, Sim In Lee, Jong Hyeon Park, Choi Kyu Park, Young Joon Ko

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Foot‐and‐mouth disease (FMD) is a highly contagious disease caused by FMD virus (FMDV) in cloven‐hoofed animals. Retinoic acid‐inducible gene I (RIG‐I) and melanoma differentiation‐associated gene 5 (MDA5) are representative receptors in the cytoplasm for the detection of viral RNA and trigger antiviral responses, leading to the production of type I interferon. Although MDA5 is a crucial receptor for sensing picornavirus RNA, the interplay between MDA5 and FMDV is relatively unknown compared to the interplay between RIG‐I and FMDV. Here, we observed that the FMDV infection inhibits MDA5 protein expression. Of the non‐structural proteins, the Lb and 3C proteinases (Lbpro and 3Cpro) were identified to be primarily responsible for this inhibition. However, the inhibition by 3Cpro was independent of proteasome, lysosome, and caspase‐dependent pathway, and was by 3C protease activity. A direct interaction between 3Cpro and MDA5 protein was observed. In conclusion, this is the first report that 3Cpro inhibits MDA5 protein expression as a mechanism to evade the innate immune response during FMDV infection. These results elucidate the pathogenesis of FMDV and provide fundamental insights for the development of a novel vaccine or therapeutic agent.

Original languageEnglish
Article number271
Pages (from-to)1-14
Number of pages14
Issue number2
StatePublished - Feb 2021


  • 3C
  • Foot‐and‐mouth disease virus
  • Innate immune response
  • MDA5
  • Non‐structural protein


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