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dc.contributor.authorMakarava, N.
dc.contributor.authorSavtchenko, R.
dc.contributor.authorLasch, P.
dc.date.accessioned2019-05-17T12:53:02Z
dc.date.available2019-05-17T12:53:02Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062022587&doi=10.1186%2fs40478-018-0597-y&partnerID=40&md5=2bf4c1377f7124915290dca591d57bb9
dc.identifier.urihttp://hdl.handle.net/10713/9058
dc.description.abstractLast decade witnessed an enormous progress in generating authentic infectious prions or PrPSc in vitro using recombinant prion protein (rPrP). Previous work established that rPrP that lacks posttranslational modification is able to support replication of highly infectious PrPSc with assistance of cofactors of polyanionic nature and/or lipids. Unexpectedly, previous studies also revealed that seeding of rPrP by brain-derived PrPSc gave rise to new prion strains with new disease phenotypes documenting loss of a strain identity upon replication in rPrP substrate. Up to now, it remains unclear whether prion strain identity can be preserved upon replication in rPrP. The current study reports that faithful replication of hamster strain SSLOW could be achieved in vitro using rPrP as a substrate. We found that a mixture of phosphatidylethanolamine (PE) and synthetic nucleic acid polyA was sufficient for stable replication of hamster brain-derived SSLOW PrPSc in serial Protein Misfolding Cyclic Amplification (sPMCA) that uses hamster rPrP as a substrate. The disease phenotype generated in hamsters upon transmission of recombinant PrPSc produced in vitro was strikingly similar to the original SSLOW diseases phenotype with respect to the incubation time to disease, as well as clinical, neuropathological and biochemical features. Infrared microspectroscopy (IR-MSP) indicated that PrPSc produced in animals upon transmission of recombinant PrPSc is structurally similar if not identical to the original SSLOW PrPSc. The current study is the first to demonstrate that rPrP can support replication of brain-derived PrPSc while preserving its strain identity. In addition, the current work is the first to document that successful propagation of a hamster strain could be achieved in vitro using hamster rPrP.en_US
dc.description.urihttps://dx.doi.org/10.1186/s40478-018-0597-yen_US
dc.language.isoen_USen_US
dc.publisherBMCen_US
dc.relation.ispartofActa neuropathologica communications
dc.subjectPrion diseasesen_US
dc.subjectPrion strainen_US
dc.subjectPrionsen_US
dc.subjectRecombinant prion proteinen_US
dc.subjectReplication cofactorsen_US
dc.titlePreserving prion strain identity upon replication of prions in vitro using recombinant prion proteinen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s40478-018-0597-y
dc.identifier.pmid30208966


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