Porcine parvovirus nonstructural protein NS1 activates NF-κB and it involves TLR2 signaling pathway

J Vet Sci. 2020 May;21(3):e50. doi: 10.4142/jvs.2020.21.e50.

Abstract

Background: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6.

Objectives: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function.

Methods: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used.

Results: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1.

Conclusions: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection.

Keywords: IL-6; NF-κB; Porcine parvovirus; toll-like receptors.

MeSH terms

  • Animals
  • Gene Expression Regulation / immunology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Parvoviridae Infections / genetics
  • Parvoviridae Infections / metabolism
  • Parvoviridae Infections / veterinary*
  • Parvovirus, Porcine / genetics
  • Parvovirus, Porcine / physiology*
  • Signal Transduction*
  • Swine
  • Swine Diseases / genetics*
  • Swine Diseases / metabolism
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism

Substances

  • NF-kappa B
  • NS1 protein, parvovirus
  • Toll-Like Receptor 2
  • Viral Nonstructural Proteins