Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3α/β Pathway

PLoS One. 2016 Aug 25;11(8):e0161508. doi: 10.1371/journal.pone.0161508. eCollection 2016.

Abstract

Porcine epidemic diarrhea virus (PEDV) has recently caused high mortality in suckling piglets with subsequent large economic losses to the swine industry. Many intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, are activated by viral infection. The PI3K/Akt pathway is an important cellular pathway that has been shown to be required for virus replication. In the present study, we found that the PEDV JS-2013 strain activated Akt in Vero cells at early (5-15 min) and late stages (8-10 h) of infection. Inhibiting PI3K, an upstream activator of Akt, enhanced PEDV replication. Inhibiting GSK-3α/β, one of the downstream effectors of PI3K/Akt pathway and regulated by Akt during PEDV infected Vero cells, also enhanced PEDV replication. Collectively, our data suggest that PI3K/Akt/GSK-3α/β signaling pathway is activated by PEDV and functions in inhibiting PEDV replication.

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / veterinary
  • Coronavirus Infections / virology*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Porcine epidemic diarrhea virus / pathogenicity*
  • Porcine epidemic diarrhea virus / physiology
  • Signal Transduction*
  • Swine
  • Swine Diseases / metabolism
  • Swine Diseases / virology
  • Vero Cells
  • Virus Replication

Substances

  • Phosphatidylinositol 3-Kinase
  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant no. 31201915) and the Shanghai Science and Technology Program for Agriculture (grant nos. 2013-5-5 and 2013-3-6).