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Murine norovirus infection of macrophages induces intrinsic apoptosis as the major form of programmed cell death.
- Source :
-
Virology . Jan2024, Vol. 589, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- 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. • MNV infection of murine macrophages induces morphological changes associated with cell death. • Chemical perturbation and cell lines deficient in pyroptosis or necroptosis pathways do not affect MNV replication. • Infection of murine macrophages with MNV results in the activation of pro-apoptotic proteins. • Induction of apoptosis is independent of caspase-8 indicating a role for intrinsic apoptosis. • Inhibition of caspases or depletion of a range of caspases results in prolonged cell survival and reduced MNV production. [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOPTOSIS
*NOROVIRUS diseases
*CELL death
*MACROPHAGES
*INFLAMMATORY mediators
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 589
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 174102424
- Full Text :
- https://doi.org/10.1016/j.virol.2023.109921