Norovirus-mediated translation repression promotes macrophage cell death

by Turgut E. Aktepe, Joshua M. Deerain, Jennifer L. Hyde, Svenja Fritzlar, Eleanor M. Mead, Julio Carrera Montoya, Abderrahman Hachani, Jaclyn S. Pearson, Peter A. White, Jason M. Mackenzie

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.