RNA Interference of Trypanosoma brucei Cathepsin B and L Affects Disease Progression in a Mouse Model

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dc.contributor.authorAbdulla, Maha-Hamadienen
dc.contributor.authorO'Brien, Theresa C.en
dc.contributor.authorMackey, Zachary B.en
dc.contributor.authorSajid, Mohameden
dc.contributor.authorGrab, Dennis J.en
dc.contributor.authorMcKerrow, James H.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2018-06-01T19:06:14Zen
dc.date.available2018-06-01T19:06:14Zen
dc.date.issued2008-09-01en
dc.description.abstractWe investigated the roles played by the cysteine proteases cathepsin B and cathepsin L (brucipain) in the pathogenesis of Trypansoma brucei brucei in both an in vivo mouse model and an in vitro model of the blood–brain barrier. Doxycycline induction of RNAi targeting cathepsin B led to parasite clearance from the bloodstream and prevent a lethal infection in the mice. In contrast, all mice infected with T. brucei containing the uninduced Trypanosoma brucei cathepsin B (TbCatB) RNA construct died by day 13. Induction of RNAi against brucipain did not cure mice from infection; however, 50% of these mice survived 60 days longer than uninduced controls. The ability of T. b. brucei to cross an in vitro model of the human blood–brain barrier was also reduced by brucipain RNAi induction. Taken together, the data suggest that while TbCatB is the more likely target for the development of new chemotherapy, a possible role for brucipain is in facilitating parasite entry into the brain.en
dc.description.versionPublished versionen
dc.format.extent? - ? (6) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pntd.0000298en
dc.identifier.issn1935-2735en
dc.identifier.issue9en
dc.identifier.orcidMackey, ZB [0000-0002-4533-0973]en
dc.identifier.urihttp://hdl.handle.net/10919/83440en
dc.identifier.volume2en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000261807500005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectInfectious Diseasesen
dc.subjectParasitologyen
dc.subjectTropical Medicineen
dc.subjectMICROVASCULAR ENDOTHELIAL-CELLSen
dc.subjectBLOOD-BRAIN-BARRIERen
dc.subjectAFRICAN TRYPANOSOMESen
dc.subjectCYSTEINE PROTEASEen
dc.subjectSTREAM FORMSen
dc.subjectIN-VITROen
dc.subjectEXPRESSIONen
dc.subjectHOSTen
dc.titleRNA Interference of Trypanosoma brucei Cathepsin B and L Affects Disease Progression in a Mouse Modelen
dc.title.serialPLoS Neglected Tropical Diseasesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen

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