Norovirus-mediated translation repression promotes macrophage cell death

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...

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Bibliographic Details
Published in:PLoS pathogens 2024-09, Vol.20 (9), p.e1012480
Main Authors: Aktepe, Turgut E, Deerain, Joshua M, Hyde, Jennifer L, Fritzlar, Svenja, Mead, Eleanor M, Carrera Montoya, Julio, Hachani, Abderrahman, Pearson, Jaclyn S, White, Peter A, Mackenzie, Jason M
Format: Article
Language:English
Subjects:
Amino acids
Animals
Antiviral agents
Apoptosis
Biochemistry
Caliciviridae Infections - virology
Cell death
Cell Death - physiology
Ethylenediaminetetraacetic acid
Genetic aspects
Genetic translation
Health aspects
Humans
Infection
Investigations
Macrophages
Macrophages - metabolism
Macrophages - virology
Mice
Norovirus
Norovirus - physiology
Physiological aspects
Protein Biosynthesis
Vaccines
Viral genetics
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Viral proteins
Virus Replication - physiology
Virus research
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1012480