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Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1.

  • Sun, Peng1, 2
  • Zhang, Shumin1
  • Qin, Xiaodong1
  • Chang, Xingni1
  • Cui, Xiaorui1
  • Li, Haitao1
  • Zhang, Shuaijun1
  • Gao, Huanhuan2
  • Wang, Penghua3
  • Zhang, Zhidong1
  • Luo, Jianxun1
  • Li, Zhiyong1
  • 1 a State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Grazing Animal Diseases of Ministry of Agriculture , Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou , Gansu , China. , (China)
  • 2 b Department of Cell Biology, School of Life Sciences , Lanzhou University , Lanzhou , Gansu , China. , (China)
  • 3 c Department of Microbiology and Immunology , New York Medical College, Valhalla , New York , USA.
Published Article
Landes Bioscience
Publication Date
Nov 23, 2017
DOI: 10.1080/15548627.2017.1405187
PMID: 29166823


Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway.

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