1887

Journal of General Virology header logo

Volume 105, Issue 8

Porcine deltacoronavirus nucleocapsid protein interacts with the Grb2 through its proline-rich motifs to induce activation of the Raf-MEK-ERK signal pathway and promote virus replication Open Access

Abstract

Porcine deltacoronavirus (PDCoV), an enteropathogenic coronavirus, causes severe watery diarrhoea, dehydration and high mortality in piglets, which has the potential for cross-species transmission in recent years. Growth factor receptor-bound protein 2 (Grb2) is a bridging protein that can couple cell surface receptors with intracellular signal transduction events. Here, we investigated the reciprocal regulation between Grb2 and PDCoV. It is found that Grb2 regulates PDCoV infection and promotes IFN-β production through activating Raf/MEK/ERK/STAT3 pathway signalling in PDCoV-infected swine testis cells to suppress viral replication. PDCoV N is capable of interacting with Grb2. The proline-rich motifs in the N- or C-terminal region of PDCoV N were critical for the interaction between PDCoV-N and Grb2. Except for PDCoV N, the PEDV N protein could interact with Grb2 and affect the regulation of PEDV replication, while the N protein of PHEV and AIBV could not interact with Grb2. PDCoV N promotes Grb2 degradation by K48- and K63-linked ubiquitin-proteasome pathways. Overexpression of PDCoV N impaired the Grb2-mediated activated effect on the Raf/MEK/ERK/STAT3 signal pathway. Thus, our study reveals a novel mechanism of how host protein Grb2 protein regulates viral replication and how PDCoV N escaped natural immunity by interacting with Grb2.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Grb2 , N protein , PDCoV , replication and ubiquitination
Funding
This study was supported by the:
  • China Agriculture Research System (Award CARS-35)
    • Principle Award Recipient: XinshengLiu
  • National Center of Technology Innovation for Pigs (Award NCTIP-XD/C 03)
    • Principle Award Recipient: XinshengLiu
  • National Natural Science Foundation of China (Award U22A20522)
    • Principle Award Recipient: XinshengLiu
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-08-13
2024-09-15
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Porcine deltacoronavirus nucleocapsid protein interacts with the Grb2 through its proline-rich motifs to induce activation of the Raf-MEK-ERK signal pathway and promote virus replication
J. Gen. Virol. 105, 002014 (2024); https://doi.org/10.1099/jgv.0.002014
/content/journal/jgv/10.1099/jgv.0.002014
/content/journal/jgv/10.1099/jgv.0.002014
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