Cellular vimentin interacts with VP70 protein of goose astrovirus genotype 2 and acts as a structural organizer to facilitate viral replication

Poult Sci. 2024 Oct;103(10):104146. doi: 10.1016/j.psj.2024.104146. Epub 2024 Jul 30.

Abstract

The fatal gouty disease caused by goose astrovirus genotype 2 (GAstV-2) still seriously endangers the goose industry in China, causing great economic losses. However, research on its infection mechanism has progressed relatively slowly. VP70 is the structural protein of GAstV-2 and is closely related to virus invasion and replication. To better understand the role of VP70 during GAstV-2 infection, we used immunoprecipitation and mass spectrometry to identify host proteins that interact with VP70. Here, we report that cellular vimentin (VIM) is a host binding partner of VP70. Site-directed mutagenesis showed that amino acid residues 399 to 413 of VP70 interacted with VIM. Using reverse genetics, we found that VP70 mutation disrupts the interaction of VP70 with VIM, which is essential for viral replication. Overexpression of VIM significantly promoted GAstV-2 replication, while knockdown of VIM significantly inhibited GAstV-2 replication. Laser confocal microscopy showed that VP70 protein expression induced the rearrangement of VIM, gradually aggregating from the original uniform grid to the side of the nucleus, and aggregated the originally dispersed GAstV-2 RNA in VIM. This rearrangement was associated with increased VIM phosphorylation caused by GAstV-2. Meanwhile, blocking VIM rearrangement with acrylamide substantially inhibited viral replication. These results indicate that VIM interacts with VP70 and positively regulates GAstV-2 replication, and VIM-VP70 interaction and an intact VIM network are needed for GAstV-2 replication. This study provides a theoretical basis and novel perspective for the further characterization of the pathogenic mechanism of GAstV-2-induced gouty disease in goslings.

Keywords: VP70 protein; goose astrovirus genotype 2; interaction; vimentin; viral replication.

MeSH terms

  • Animals
  • Astroviridae Infections / veterinary
  • Astroviridae Infections / virology
  • Avastrovirus* / genetics
  • Avastrovirus* / metabolism
  • Avastrovirus* / physiology
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Geese* / virology
  • Genotype
  • Poultry Diseases* / virology
  • Vimentin* / genetics
  • Vimentin* / metabolism
  • Virus Replication*

Substances

  • Vimentin
  • Avian Proteins