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Abstract

Infection with the porcine epidemic diarrhoea virus (PEDV) causes severe enteric disease in suckling piglets, causing massive economic losses in the swine industry worldwide. Tripartite motif-containing 56 (TRIM56) has been shown to augment type I IFN response, but whether it affects PEDV replication remains uncharacterized. Here we investigated the role of TRIM56 in Marc-145 cells during PEDV infection. We found that TRIM56 expression was upregulated in cells infected with PEDV. Overexpression of TRIM56 effectively reduced PEDV replication, while knockdown of TRIM56 resulted in increased viral replication. TRIM56 overexpression significantly increased the phosphorylation of IRF3 and NF-κB P65, and enhanced the IFN-β antiviral response, while silencing TRIM56 did not affect IRF3 activation. TRIM56 overexpression increased the protein level of TRAF3, the component of the TLR3 pathway, thereby significantly activating downstream IRF3 and NF-κB signalling. We demonstrated that TRIM56 overexpression inhibited PEDV replication and upregulated expression of IFN-β, IFN-stimulated genes (ISGs) and chemokines in a dose-dependent manner. Moreover, truncations of the RING domain, N-terminal domain or C-terminal portion on TRIM56 were unable to induce IFN-β expression and failed to restrict PEDV replication. Together, our results suggested that TRIM56 was upregulated in Marc-145 cells in response to PEDV infection. Overexpression of TRIM56 inhibited PEDV replication by positively regulating the TLR3-mediated antiviral signalling pathway. These findings provide evidence that TRIM56 plays a positive role in the innate immune response during PEDV infection.

Keyword(s): IFN-β , ISGs , PEDV , TRAF3 and TRIM56
Funding
This study was supported by the:
  • Agriculture Department of Shaanxi Province (Award 2019NY-081)
    • Principle Award Recipient: qizhang
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/content/journal/jgv/10.1099/jgv.0.001748
2022-05-03
2024-12-10
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