Norovirus-mediated translation repression promotes macrophage cell death

PLoS Pathog. 2024 Sep 3;20(9):e1012480. doi: 10.1371/journal.ppat.1012480. eCollection 2024 Sep.

Abstract

Norovirus infection is characterised by a rapid onset of disease and the development of debilitating symptoms including projectile vomiting and diffuse diarrhoea. Vaccines and antivirals are sorely lacking and developments in these areas are hampered by the lack of an adequate cell culture system to investigate human norovirus replication and pathogenesis. Herein, we describe how the model norovirus, Mouse norovirus (MNV), produces a viral protein, NS3, with the functional capacity to attenuate host protein translation which invokes the activation of cell death via apoptosis. We show that this function of NS3 is conserved between human and mouse viruses and map the protein domain attributable to this function. Our study highlights a critical viral protein that mediates crucial activities during replication, potentially identifying NS3 as a worthy target for antiviral drug development.

MeSH terms

  • Animals
  • Apoptosis
  • Caliciviridae Infections* / virology
  • Cell Death / physiology
  • Humans
  • Macrophages* / metabolism
  • Macrophages* / virology
  • Mice
  • Norovirus* / physiology
  • Protein Biosynthesis
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / physiology

Substances

  • Viral Nonstructural Proteins

Grants and funding

JMM and PAW were funded by the National Health and Medical Research Council of Australia, grant number 1123135. JMD was supported by a PhD stipend provided by the University of Melbourne and the Miller Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.