Expression of the murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in a virus-free cell model
| Autor: | Morgan R, Herod, Omar, Salim, Rachel J, Skilton, Cynthia A, Prince, Vernon K, Ward, Paul R, Lambden, Ian N, Clarke |
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| Rok vydání: | 2013 |
| Předmět: |
viruses
Blotting Western Apoptosis Genome Viral Pathogenesis Models Biological Microbiology Mice Viral Proteins Virology Molecular Cell Biology Animals Humans Signaling in Cellular Processes Biology Polyproteins Apoptotic Signaling Norovirus biochemical phenomena metabolism and nutrition Tetracycline Viral Replication Clone Cells HEK293 Cells Eukaryotic Cells Viral Enzymes RNA Viral Cellular Types Genetic Engineering Viral Transmission and Infection Research Article Biotechnology Signal Transduction |
| Zdroj: | PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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