Deerain, J.M.* ; Aktepe, T.E.* ; Trenerry, A.M.* ; Ebert, G. ; Hyde, J.L.* ; Charry, K.* ; Edgington-Mitchell, L.* ; Xu, B.* ; Ambrose, R.L.* ; Sarvestani, S.T.* ; Lawlor, K.E.* ; Pearson, J.S.* ; White, P.A.* ; Mackenzie, J.M.*
Murine norovirus infection of macrophages induces intrinsic apoptosis as the major form of programmed cell death.
Virology 589:12 (2024)
Human norovirus is the leading cause of acute gastroenteritis worldwide, however despite the significance of this pathogen, we have a limited understanding of how noroviruses cause disease, and modulate the innate immune response. Programmed cell death (PCD) is an important part of the innate response to invading pathogens, but little is known about how specific PCD pathways contribute to norovirus replication. Here, we reveal that murine norovirus (MNV) virus-induced PCD in macrophages correlates with the release of infectious virus. We subsequently show, genetically and chemically, that MNV-induced cell death and viral replication occurs independent of the activity of inflammatory mediators. Further analysis revealed that MNV infection promotes the cleavage of apoptotic caspase-3 and PARP. Correspondingly, pan-caspase inhibition, or BAX and BAK deficiency, perturbed viral replication rates and delayed virus release and cell death. These results provide new insights into how MNV harnesses cell death to increase viral burden.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Norovirus; Murine norovirus; Apoptosis; Programmed cell death; Macrophage
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Language
english
Publication Year
2024
Prepublished in Year
2023
HGF-reported in Year
2023
ISSN (print) / ISBN
0042-6822
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0042-6822
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Article Number: 12
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Elsevier
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525 B St, Ste 1900, San Diego, Ca 92101-4495 Usa
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-502700-010
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Erfassungsdatum
2024-01-15