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 b...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3944349?pdf=render |
| _version_ | 1811290818872344576 |
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| author | Morgan R Herod Omar Salim Rachel J Skilton Cynthia A Prince Vernon K Ward Paul R Lambden Ian N Clarke |
| author_facet | Morgan R Herod Omar Salim Rachel J Skilton Cynthia A Prince Vernon K Ward Paul R Lambden Ian N Clarke |
| author_sort | Morgan R Herod |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T04:20:10Z |
| format | Article |
| id | doaj.art-2bb8d2b4de25413f84d7066b538b8b0e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T04:20:10Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2bb8d2b4de25413f84d7066b538b8b0e2022-12-22T03:02:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9067910.1371/journal.pone.0090679Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model.Morgan R HerodOmar SalimRachel J SkiltonCynthia A PrinceVernon K WardPaul R LambdenIan N ClarkeInvestigations 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.http://europepmc.org/articles/PMC3944349?pdf=render |
| spellingShingle | Morgan R Herod Omar Salim Rachel J Skilton Cynthia A Prince Vernon K Ward Paul R Lambden Ian N Clarke Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. PLoS ONE |
| title | Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. |
| title_full | Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. |
| title_fullStr | Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. |
| title_full_unstemmed | Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. |
| title_short | Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model. |
| title_sort | expression of the murine norovirus mnv orf1 polyprotein is sufficient to induce apoptosis in a virus free cell model |
| url | http://europepmc.org/articles/PMC3944349?pdf=render |
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