Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-8 expression through TAK-1/JNK/AP-1 pathways

Virology. 2017 Jun:506:64-72. doi: 10.1016/j.virol.2017.03.009. Epub 2017 Mar 24.

Abstract

The acute phase of respiratory distress caused by porcine reproductive and respiratory syndrome virus (PRRSV) is likely a consequence of the release of inflammatory cytokines in the lung. IL-8, the main chemokine and activator of neutrophils, might be related to the lung injury upon PRRSV infection. In this study, we showed that PRRSV induced IL-8 expression in vivo and in vitro. Subsequently, we demonstrated that JNK and NF-κB pathways were activated upon PRRSV infection and required for the enhancement of IL-8 expression. We further verified that PRRSV-activated TAK-1 was essential for the activation of JNK and NF-κB pathways and IL-8 expression. Moreover, we revealed an AP-1 binding motif in the cloned porcine IL-8 (pIL-8) promoter, and deletion of this motif abolished the pIL-8 promoter activity. Finally, we found that the JNK-activated AP-1 subunit c-Jun was critical for the up-regulation of IL-8 expression by PRRSV. These data suggest that PRRSV-induced IL-8 production is likely through the TAK-1/JNK/AP-1 pathways.

Keywords: AP-1; IL-8; JNK; PRRSV; TAK-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Interleukin-8 / genetics*
  • Interleukin-8 / immunology
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Porcine Reproductive and Respiratory Syndrome / enzymology
  • Porcine Reproductive and Respiratory Syndrome / genetics*
  • Porcine Reproductive and Respiratory Syndrome / metabolism
  • Porcine Reproductive and Respiratory Syndrome / virology
  • Porcine respiratory and reproductive syndrome virus
  • Signal Transduction
  • Swine
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Up-Regulation

Substances

  • Interleukin-8
  • Transcription Factor AP-1
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7