PGAM5 degrades PDCoV N protein and activates type I interferon to antagonize viral replication

J Virol. 2023 Nov 30;97(11):e0147023. doi: 10.1128/jvi.01470-23. Epub 2023 Oct 26.

Abstract

As a member of the δ-coronavirus family, porcine deltacoronavirus (PDCoV) is a vital reason for diarrhea in piglets, which can contribute to high morbidity and mortality rates. Initially identified in Hong Kong in 2012, the virus has rapidly spread worldwide. During PDCoV infection, the virus employs evasion mechanisms to evade host surveillance, while the host mounts corresponding responses to impede viral replication. Our research has revealed that PDCoV infection down-regulates the expression of PGAM5 to promote virus replication. In contrast, PGAM5 degrades PDCoV N through autophagy by interacting with the cargo receptor P62 and the E3 ubiquitination ligase STUB1. Additionally, PGAM5 interacts with MyD88 and TRAF3 to activate the IFN signal pathway, resulting in the inhibition of viral replication.

Keywords: N protein; PDCoV; PGAM5; autophagy; type I interferon.

MeSH terms

  • Animals
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / veterinary
  • Coronavirus Infections* / virology
  • Coronavirus Nucleocapsid Proteins* / metabolism
  • Deltacoronavirus* / immunology
  • Deltacoronavirus* / metabolism
  • Down-Regulation
  • Immune Evasion
  • Interferon Type I* / immunology
  • Mitochondrial Proteins* / metabolism
  • Phosphoprotein Phosphatases* / metabolism
  • Proteolysis*
  • RNA-Binding Proteins / metabolism
  • Signal Transduction
  • Swine Diseases* / virology
  • Swine* / virology
  • Ubiquitin-Protein Ligases / metabolism
  • Virus Replication* / immunology

Substances

  • Interferon Type I
  • Ubiquitin-Protein Ligases
  • Coronavirus Nucleocapsid Proteins
  • Phosphoprotein Phosphatases
  • Mitochondrial Proteins
  • RNA-Binding Proteins