Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation

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cg.authorship.typesCGIAR and advanced research instituteen
cg.contributor.affiliationUniversity of Marylanden
cg.contributor.affiliationUniversité de Paris Descartesen
cg.contributor.affiliationCochin Instituteen
cg.contributor.affiliationWashington State Universityen
cg.contributor.affiliationKing Abdullah University of Science and Technologyen
cg.contributor.affiliationUnited States Department of Agricultureen
cg.contributor.affiliationWeizmann Institute of Scienceen
cg.contributor.affiliationInternational Livestock Research Instituteen
cg.contributor.affiliationBar-Ilan Universityen
cg.contributor.affiliationSwiss Tropical and Public Health Instituteen
cg.contributor.affiliationUniversity of Baselen
cg.contributor.crpLivestock
cg.contributor.donorUnited States Department of Agricultureen
cg.contributor.donorNorman Borlaug Commemorative Research Initiativeen
cg.contributor.donorUnited States Agency for International Developmenten
cg.contributor.donorDepartment for International Development, United Kingdomen
cg.contributor.donorBill & Melinda Gates Foundationen
cg.creator.identifierVishvanath Nene: 0000-0001-7066-4169
cg.creator.identifierRichard Bishop: 0000-0002-3720-9970
cg.creator.identifierClaudia Daubenberger: 0000-0001-7136-0642
cg.howPublishedFormally Publisheden
cg.identifier.doihttps://doi.org/10.1038/s41598-020-60939-xen
cg.isijournalISI Journalen
cg.issn2045-2322en
cg.issue1en
cg.journalScientific Reportsen
cg.reviewStatusPeer Reviewen
cg.speciesTheileria parvaen
cg.subject.ilriANIMAL DISEASESen
cg.subject.ilriCATTLEen
cg.subject.ilriDISEASE CONTROLen
cg.subject.ilriECFen
cg.subject.ilriLIVESTOCKen
cg.subject.ilriVACCINESen
cg.volume10en
dc.contributor.authorTretina, Kyleen
dc.contributor.authorHaidar, M.en
dc.contributor.authorMadsen-Bouterse, S.A.en
dc.contributor.authorSakura, T.en
dc.contributor.authorMfarrej, S.en
dc.contributor.authorFry, L.M.en
dc.contributor.authorChaussepied, M.en
dc.contributor.authorPain, A.en
dc.contributor.authorKnowles, Donald P.en
dc.contributor.authorNene, Vishvanath M.en
dc.contributor.authorGinsberg, D.en
dc.contributor.authorDaubenberger, C.A.en
dc.contributor.authorBishop, Richard P.en
dc.contributor.authorLangsley, G.en
dc.contributor.authorSilva, Joana C.en
dc.date.accessioned2020-04-29T13:47:57Zen
dc.date.available2020-04-29T13:47:57Zen
dc.identifier.urihttps://hdl.handle.net/10568/108093
dc.titleTheileria parasites subvert E2F signaling to stimulate leukocyte proliferationen
dcterms.abstractIntracellular 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.en
dcterms.accessRightsOpen Access
dcterms.audienceScientistsen
dcterms.available2020-03-04
dcterms.bibliographicCitationTretina, 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.en
dcterms.issued2020-03-04
dcterms.languageen
dcterms.licenseCC-BY-4.0
dcterms.publisherSpringeren
dcterms.subjecttheileriaen
dcterms.subjectcattleen
dcterms.subjectanimal diseasesen
dcterms.subjectvaccinesen
dcterms.subjectdisease controlen
dcterms.subjecteast coast feveren
dcterms.typeJournal Article

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