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Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and

Huan Wang1, Dingxiang Liu2, Yingjie Sun1

  • 1Waterfowl Viral Infectious Diseases Team, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P. R. China.

Veterinary Research
|January 12, 2021
PubMed

Insights

Infectious bronchitis virus (IBV) activates the ERK pathway, which promotes viral replication. Upregulation of DUSP6 creates a negative feedback loop, restricting virus growth and increasing cell death, suggesting ERK pathway components as antiviral targets.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Understanding virus-cell interactions is key for antiviral therapies.
  • The ERK pathway's role in coronavirus infection, specifically IBV, remains unclear.

Purpose of the Study:

  • To investigate the role of the ERK1/2 signaling pathway in Infectious Bronchitis Virus (IBV) infection.
  • To elucidate the interplay between IBV, ERK1/2 signaling, and DUSP6.

Main Methods:

  • Examined ERK1/2 activation and DUSP6 expression during IBV infection.
  • Utilized pharmacological inhibitors and siRNA to modulate MEK1/2-ERK1/2 signaling and DUSP6.
  • Assessed apoptosis and viral replication under different signaling conditions.

Main Results:

  • IBV infection activated ERK1/2 signaling, with DUSP6 upregulation forming a negative feedback loop.
  • Inhibiting MEK1/2-ERK1/2 signaling restricted viral replication but increased cell death.
  • Suppressing DUSP6 enhanced ERK1/2 activity, protected cells from apoptosis, and facilitated IBV replication.

Conclusions:

  • The MEK-ERK1/2 pathway promotes IBV infection by enhancing cell survival.
  • DUSP6 induction acts as a negative regulator, correlating with reduced viral load and increased apoptosis.
  • MEK1/2 and DUSP6 are potential therapeutic targets for developing antivirals against IBV.
Keywords:
DUSP6ERK1/2IBVvirus replication

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