NDV related exosomes enhance NDV replication through exporting NLRX1 mRNA

Vet Microbiol. 2021 Sep:260:109167. doi: 10.1016/j.vetmic.2021.109167. Epub 2021 Jun 29.

Abstract

Virulent Newcastle disease virus (NDV) is a violent infection in avian species. The understanding of its pathogenic mechanism is consistently evolving along with the development of molecular biological advancement. Exosomes derived from NDV infected cells (NDV Ex) were reported to promote virus replication through transportation of viral proteins and miRNAs. However, the function of mRNAs in NDV Ex remains unknown. In this study, a novel mechanism of NDV Ex to facilitate NDV infection was explored. Through transcriptome analysis, seven immune related genes were found to up-regulate in NDV Ex. Among them, NLRX1 mRNA was notably enriched in NDV Ex, and decreased inside the cells after virulent NDV infection. Further investigation suggested that NLRX1 mRNA decrease was in accordance with the NLRX1 protein expression reduction. This process can be reversed by the inhibition of exosome release. Therefore, NDV infection could utilize NDV Ex to export NLRX1 mRNA and reduce cellular NLRX1 protein. As NLRX1 is a crucial anti-viral protein of MAVS signal pathway, and NDV Ex transported NLRX1 cannot counteract its function in recipient cells, it can be concluded that NDV could benefit its replication through exporting NLRX1 mRNA to relieve the anti-viral pressure on its survival.

Keywords: Exosome mediated exportation; Exosomes; MAVS signal pathway; NLRX1; Newcastle disease virus.

MeSH terms

  • Animals
  • Biological Transport
  • Chick Embryo
  • Exosomes / metabolism*
  • Fibroblasts / virology
  • HeLa Cells
  • Humans
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Newcastle Disease / virology*
  • Newcastle disease virus / genetics
  • Newcastle disease virus / pathogenicity*
  • Newcastle disease virus / physiology
  • RNA, Messenger / genetics
  • Signal Transduction*
  • Specific Pathogen-Free Organisms
  • Transcriptome*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Replication

Substances

  • Mitochondrial Proteins
  • NLRX1 protein, human
  • RNA, Messenger
  • Viral Proteins