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2018-09-12Zeitschriftenartikel DOI: 10.25646/5719
Preserving prion strain identity upon replication of prions in vitro using recombinant prion protein
dc.contributor.authorMakarava, Natallia
dc.contributor.authorSavtchenko, Regina
dc.contributor.authorLasch, Peter
dc.contributor.authorBeekes, Michael
dc.contributor.authorBaskakov, Ilia V.
dc.date.accessioned2018-10-01T08:35:07Z
dc.date.available2018-10-01T08:35:07Z
dc.date.issued2018-09-12none
dc.identifier.other10.1186/s40478-018-0597-y
dc.identifier.urihttp://edoc.rki.de/176904/5780
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.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectPrionseng
dc.subjectPrion diseaseseng
dc.subjectPrion straineng
dc.subjectReplication cofactorseng
dc.subjectRecombinant prion proteineng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titlePreserving prion strain identity upon replication of prions in vitro using recombinant prion proteinnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:0257-176904/5780-8
dc.identifier.doihttp://dx.doi.org/10.25646/5719
dc.type.versionpublishedVersionnone
local.edoc.container-titleActa Neuropathologica Communicationsnone
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-018-0597-ynone
local.edoc.container-publisher-nameBioMedCentralnone
local.edoc.container-volume6none
local.edoc.container-issue92none
local.edoc.container-reportyear2018none
local.edoc.container-firstpage1none
local.edoc.container-lastpage14none
local.edoc.rki-departmentZentrum für Biologische Gefahren und Spezielle Pathogenenone
dc.description.versionPeer Reviewednone

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