Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation
Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the im...
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | Journal Article |
| Lenguaje: | Inglés |
| Publicado: |
Springer
2020
|
| Materias: | |
| Acceso en línea: | https://hdl.handle.net/10568/108093 |
| _version_ | 1855536767425314816 |
|---|---|
| author | Tretina, Kyle Haidar, M. Madsen-Bouterse, S.A. Sakura, T. Mfarrej, S. Fry, L.M. Chaussepied, M. Pain, A. Knowles, Donald P. Nene, Vishvanath M. Ginsberg, D. Daubenberger, C.A. Bishop, Richard P. Langsley, G. Silva, Joana C. |
| author_browse | Bishop, Richard P. Chaussepied, M. Daubenberger, C.A. Fry, L.M. Ginsberg, D. Haidar, M. Knowles, Donald P. Langsley, G. Madsen-Bouterse, S.A. Mfarrej, S. Nene, Vishvanath M. Pain, A. Sakura, T. Silva, Joana C. Tretina, Kyle |
| author_facet | Tretina, Kyle Haidar, M. Madsen-Bouterse, S.A. Sakura, T. Mfarrej, S. Fry, L.M. Chaussepied, M. Pain, A. Knowles, Donald P. Nene, Vishvanath M. Ginsberg, D. Daubenberger, C.A. Bishop, Richard P. Langsley, G. Silva, Joana C. |
| author_sort | Tretina, Kyle |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation. Using comparative genomics and surface plasmon resonance, we identified parasite-derived peptides that have the sequence-specific ability to increase E2F signaling by binding E2F negative regulator Retinoblastoma-1 (RB). Using these peptides as a tool to probe host E2F signaling, we show that the disruption of RB complexes ex vivo leads to activation of E2F-driven transcription and increased leukocyte proliferation in an infection-dependent manner. This result is consistent with existing models and, together, they support a critical role of E2F signaling for Theileria-induced host cell proliferation, and its potential direct manipulation by one or more parasite proteins. |
| format | Journal Article |
| id | CGSpace108093 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | Springer |
| publisherStr | Springer |
| record_format | dspace |
| spelling | CGSpace1080932024-05-01T08:19:11Z Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation Tretina, Kyle Haidar, M. Madsen-Bouterse, S.A. Sakura, T. Mfarrej, S. Fry, L.M. Chaussepied, M. Pain, A. Knowles, Donald P. Nene, Vishvanath M. Ginsberg, D. Daubenberger, C.A. Bishop, Richard P. Langsley, G. Silva, Joana C. theileria cattle animal diseases vaccines disease control east coast fever Intracellular pathogens have evolved intricate mechanisms to subvert host cell signaling pathways and ensure their own propagation. A lineage of the protozoan parasite genus Theileria infects bovine leukocytes and induces their uncontrolled proliferation causing a leukemia-like disease. Given the importance of E2F transcription factors in mammalian cell cycle regulation, we investigated the role of E2F signaling in Theileria-induced host cell proliferation. Using comparative genomics and surface plasmon resonance, we identified parasite-derived peptides that have the sequence-specific ability to increase E2F signaling by binding E2F negative regulator Retinoblastoma-1 (RB). Using these peptides as a tool to probe host E2F signaling, we show that the disruption of RB complexes ex vivo leads to activation of E2F-driven transcription and increased leukocyte proliferation in an infection-dependent manner. This result is consistent with existing models and, together, they support a critical role of E2F signaling for Theileria-induced host cell proliferation, and its potential direct manipulation by one or more parasite proteins. 2020-03-04 2020-04-29T13:47:57Z 2020-04-29T13:47:57Z Journal Article https://hdl.handle.net/10568/108093 en Open Access Springer Tretina, K., Haidar, M., Madsen-Bouterse, S.A., Sakura, T., Mfarrej, S., Fry, L., Chaussepied, M., Pain, A., Knowles, D.P., Nene, V.M., Ginsberg, D., Daubenberger, C.A., Bishop, R.P., Langsley, G. and Silva, J.C. 2020. Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation. Scientific Reports 10: 3982. |
| spellingShingle | theileria cattle animal diseases vaccines disease control east coast fever Tretina, Kyle Haidar, M. Madsen-Bouterse, S.A. Sakura, T. Mfarrej, S. Fry, L.M. Chaussepied, M. Pain, A. Knowles, Donald P. Nene, Vishvanath M. Ginsberg, D. Daubenberger, C.A. Bishop, Richard P. Langsley, G. Silva, Joana C. Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation |
| title | Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation |
| title_full | Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation |
| title_fullStr | Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation |
| title_full_unstemmed | Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation |
| title_short | Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation |
| title_sort | theileria parasites subvert e2f signaling to stimulate leukocyte proliferation |
| topic | theileria cattle animal diseases vaccines disease control east coast fever |
| url | https://hdl.handle.net/10568/108093 |
| work_keys_str_mv | AT tretinakyle theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT haidarm theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT madsenboutersesa theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT sakurat theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT mfarrejs theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT frylm theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT chaussepiedm theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT paina theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT knowlesdonaldp theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT nenevishvanathm theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT ginsbergd theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT daubenbergerca theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT bishoprichardp theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT langsleyg theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation AT silvajoanac theileriaparasitessubverte2fsignalingtostimulateleukocyteproliferation |