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Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model

Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model
Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model
Investigations into human norovirus infection, replication and pathogenesis, as well as the development of potential antiviral agents, have been restricted by the lack of a cell culture system for human norovirus. To date, the optimal cell culture surrogate virus model for studying human norovirus biology is the murine norovirus (MNV). In this report we generate a tetracycline-regulated, inducible eukaryotic cell system expressing the entire MNV ORF1 polyprotein. Once induced, the MNV ORF1 polyprotein was faithfully processed to the six mature non-structural proteins that predominately located to a discrete perinuclear region, as has been observed in active MNV infection. Furthermore, we found that expression of the ORF1 polyprotein alone was sufficient to induce apoptosis, characterised by caspase-9 activation and survivin down-regulation. This cell line provides a valuable new tool for studying MNV ORF1 non-structural protein function, screening for potential antiviral agents and acts as a proof-of-principle for such systems to be developed for human noroviruses
1932-6203
e90679
Herod, Morgan R.
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Salim, Omar
a8a00604-9e57-4638-8c96-5b37e75fee90
Skilton, Rachel J.
b02d4f32-609c-4074-b616-ec819b018dbe
Prince, Cynthia A.
edd6f83d-054d-4544-8777-593c80c3207a
Ward, Vernon K.
3dbf2165-fec7-437f-af39-693ea61ca31f
Lambden, Paul R.
4fcd536e-2d9a-4366-97c6-386e6b005698
Clarke, Ian N.
ff6c9324-3547-4039-bb2c-10c0b3327a8b
Herod, Morgan R.
8f27d0e7-1226-44b8-92dc-234b0da4c141
Salim, Omar
a8a00604-9e57-4638-8c96-5b37e75fee90
Skilton, Rachel J.
b02d4f32-609c-4074-b616-ec819b018dbe
Prince, Cynthia A.
edd6f83d-054d-4544-8777-593c80c3207a
Ward, Vernon K.
3dbf2165-fec7-437f-af39-693ea61ca31f
Lambden, Paul R.
4fcd536e-2d9a-4366-97c6-386e6b005698
Clarke, Ian N.
ff6c9324-3547-4039-bb2c-10c0b3327a8b

Herod, Morgan R., Salim, Omar, Skilton, Rachel J., Prince, Cynthia A., Ward, Vernon K., Lambden, Paul R. and Clarke, Ian N. (2014) Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. PLoS ONE, 9 (3), e90679. (doi:10.1371/journal.pone.0090679). (PMID:15562321)

Record type: Article

Abstract

Investigations into human norovirus infection, replication and pathogenesis, as well as the development of potential antiviral agents, have been restricted by the lack of a cell culture system for human norovirus. To date, the optimal cell culture surrogate virus model for studying human norovirus biology is the murine norovirus (MNV). In this report we generate a tetracycline-regulated, inducible eukaryotic cell system expressing the entire MNV ORF1 polyprotein. Once induced, the MNV ORF1 polyprotein was faithfully processed to the six mature non-structural proteins that predominately located to a discrete perinuclear region, as has been observed in active MNV infection. Furthermore, we found that expression of the ORF1 polyprotein alone was sufficient to induce apoptosis, characterised by caspase-9 activation and survivin down-regulation. This cell line provides a valuable new tool for studying MNV ORF1 non-structural protein function, screening for potential antiviral agents and acts as a proof-of-principle for such systems to be developed for human noroviruses

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Published date: 2014
Organisations: Faculty of Medicine

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Local EPrints ID: 363753
URI: http://eprints.soton.ac.uk/id/eprint/363753
ISSN: 1932-6203
PURE UUID: 0126ebfb-bea6-45f7-8aa0-24f16de6d3bf
ORCID for Omar Salim: ORCID iD orcid.org/0000-0002-2562-4827
ORCID for Ian N. Clarke: ORCID iD orcid.org/0000-0002-4938-1620

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Date deposited: 03 Apr 2014 09:11
Last modified: 18 Feb 2021 16:56

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Contributors

Author: Morgan R. Herod
Author: Omar Salim ORCID iD
Author: Rachel J. Skilton
Author: Cynthia A. Prince
Author: Vernon K. Ward
Author: Paul R. Lambden
Author: Ian N. Clarke ORCID iD

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