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...

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Bibliographic Details
Published in:PloS one 2014-03, Vol.9 (3), p.e90679-e90679
Main Authors: Herod, Morgan R, Salim, Omar, Skilton, Rachel J, Prince, Cynthia A, Ward, Vernon K, Lambden, Paul R, Clarke, Ian N
Format: Article
Language:English
Subjects:
Analysis
Animals
Antibiotics
Antiviral agents
Apoptosis
Apoptosis - drug effects
Biology
Blotting, Western
Cell culture
Clone Cells
Genome, Viral - genetics
Genomes
Health aspects
HEK293 Cells
Hepatitis
Humans
Infection
Infections
Localization
Mice
Models, Biological
Norovirus - metabolism
Pathogenesis
Polyproteins - metabolism
Proteins
Reading
RNA, Viral - metabolism
Studies
Tetracycline - pharmacology
Viral infections
Viral Proteins - metabolism
Virology
Viruses
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0090679