Cysteine protease activation and apoptosis in Murine norovirus infection
<p>Abstract</p> <p>Background</p> <p>Noroviruses are the leading cause of viral gastroenteritis. Because a suitable <it>in vitro </it>culture system for the human virus has yet to be developed, many basic details of the infection process are unknown. Murine...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-09-01
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| Series: | Virology Journal |
| Online Access: | http://www.virologyj.com/content/6/1/139 |
| _version_ | 1818665364817444864 |
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| author | Ettayebi Khalil Petersen Lena K Maaty Walid S Furman Linnzi M Hardy Michele E Bothner Brian |
| author_facet | Ettayebi Khalil Petersen Lena K Maaty Walid S Furman Linnzi M Hardy Michele E Bothner Brian |
| author_sort | Ettayebi Khalil |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Noroviruses are the leading cause of viral gastroenteritis. Because a suitable <it>in vitro </it>culture system for the human virus has yet to be developed, many basic details of the infection process are unknown. Murine norovirus (MNV) serves as a model system for the study of norovirus infection. Recently it was shown that infection of RAW 264.7 cells involved a novel apoptotic pathway involving survivin.</p> <p>Results</p> <p>Using a different set of approaches, the up-regulation of caspases, DNA condensation/fragmentation, and membrane blebbing, all of which are markers of apoptosis, were confirmed. Live cell imaging and activity-based protein profiling showed that activation of caspase-like proteases occurred within two hours of infection, followed by morphological changes to the cells. MNV infection in the presence of caspase inhibitors proceeded via a distinct pathway of rapid cellular necrosis and reduced viral production. Affinity purification of activity-based protein profiling targets and identification by peptide mass fingerprinting showed that the cysteine protease cathepsin B was activated early in infection, establishing this protein as an upstream activator of the intrinsic apoptotic pathway.</p> <p>Conclusion</p> <p>This work adds cathepsin B to the noncanonical programmed cell death induced by MNV, and provides data suggesting that the virus may induce apoptosis to expand the window of time for viral replication. This work also highlights the significant power of activity-based protein profiling in the study of viral pathogenesis.</p> |
| first_indexed | 2024-12-17T05:47:28Z |
| format | Article |
| id | doaj.art-573f7cf71c56443b99c9fb9d9f1cbe46 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-12-17T05:47:28Z |
| publishDate | 2009-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-573f7cf71c56443b99c9fb9d9f1cbe462022-12-21T22:01:17ZengBMCVirology Journal1743-422X2009-09-016113910.1186/1743-422X-6-139Cysteine protease activation and apoptosis in Murine norovirus infectionEttayebi KhalilPetersen Lena KMaaty Walid SFurman Linnzi MHardy Michele EBothner Brian<p>Abstract</p> <p>Background</p> <p>Noroviruses are the leading cause of viral gastroenteritis. Because a suitable <it>in vitro </it>culture system for the human virus has yet to be developed, many basic details of the infection process are unknown. Murine norovirus (MNV) serves as a model system for the study of norovirus infection. Recently it was shown that infection of RAW 264.7 cells involved a novel apoptotic pathway involving survivin.</p> <p>Results</p> <p>Using a different set of approaches, the up-regulation of caspases, DNA condensation/fragmentation, and membrane blebbing, all of which are markers of apoptosis, were confirmed. Live cell imaging and activity-based protein profiling showed that activation of caspase-like proteases occurred within two hours of infection, followed by morphological changes to the cells. MNV infection in the presence of caspase inhibitors proceeded via a distinct pathway of rapid cellular necrosis and reduced viral production. Affinity purification of activity-based protein profiling targets and identification by peptide mass fingerprinting showed that the cysteine protease cathepsin B was activated early in infection, establishing this protein as an upstream activator of the intrinsic apoptotic pathway.</p> <p>Conclusion</p> <p>This work adds cathepsin B to the noncanonical programmed cell death induced by MNV, and provides data suggesting that the virus may induce apoptosis to expand the window of time for viral replication. This work also highlights the significant power of activity-based protein profiling in the study of viral pathogenesis.</p>http://www.virologyj.com/content/6/1/139 |
| spellingShingle | Ettayebi Khalil Petersen Lena K Maaty Walid S Furman Linnzi M Hardy Michele E Bothner Brian Cysteine protease activation and apoptosis in Murine norovirus infection Virology Journal |
| title | Cysteine protease activation and apoptosis in Murine norovirus infection |
| title_full | Cysteine protease activation and apoptosis in Murine norovirus infection |
| title_fullStr | Cysteine protease activation and apoptosis in Murine norovirus infection |
| title_full_unstemmed | Cysteine protease activation and apoptosis in Murine norovirus infection |
| title_short | Cysteine protease activation and apoptosis in Murine norovirus infection |
| title_sort | cysteine protease activation and apoptosis in murine norovirus infection |
| url | http://www.virologyj.com/content/6/1/139 |
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