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dc.contributor.advisorBartz, Jasonen_US
dc.contributor.authorEckland, Thomas E.en_US
dc.date.accessioned2018-05-10T13:23:33Z
dc.date.available2018-05-10T13:23:33Z
dc.date.issued2018-05-07en_US
dc.identifier.urihttp://hdl.handle.net/10504/117879
dc.description.abstractPrion diseases are caused by a misfolded isoform of the prion protein, PrPSc. Prion strains are hypothesized to be encoded by strain-specific conformations of PrPSc. Prion strains can interfere with each other when a long incubation period strain (i.e. blocking strain) inhibits the replication of a short incubation period strain (i.e. non-blocking). Prion strain interference influences prion strain dynamics and the emergence of a strain from a mixture; however, it is unknown if two long incubation period strains can interfere with each other. Co-infection of animals with combinations of long incubation period strains failed to identify evidence of strain interference. To exclude the possibility that this inability to interfere in vivo was due to a failure to infect common a population of neurons we used protein misfolding strain interference (PMCAsi). Consistent with the animal bioassay studies we found evidence, using PMCAsi, that both co-infecting strains were amplifying independently, suggesting that the lack of strain interference is not due to a failure to target the same cells but is an inherent property of the strains involved. Additionally, we found relatively higher levels of remaining PrPC following PMCA seeded with long incubation period strains compared to short incubation period strains and hypothesize that the failure of these slowly replicating prion strains to interfere with each other in vivo or in vitro is that PrPC is not rate limiting. Overall, this observation changes the paradigm of the interactions of prion strains in a mixture and has implications for interspecies transmission and emergence of prion strains from a mixture.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.titleThe Role of PrPC and Strain Conversion Efficiency in Prion Strain Interferenceen_US
dc.typeDissertation
dc.rights.holderThomas Ecklanden_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.contributor.cuauthorEckland, Thomas E.en_US
dc.degree.levelPhD (Doctor of Philosophy)en_US
dc.degree.disciplineMedical Microbiology and Immunology (graduate program)en_US
dc.degree.namePh.D. in Medical Microbiology and Immunologyen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeBartlet-Hunt, Shannonen_US
dc.degree.committeeChen, Xian-Mingen_US
dc.degree.committeeKincaid, Anthonyen_US
dc.degree.committeeSoto, Patriciaen_US
dc.degree.committeeSwanson, Patricken_US


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