2019
Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration
Szigeti‐Buck K, Manuelidis L. Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration. Journal Of Cellular Biochemistry 2019, 120: 17687-17698. PMID: 31231867, DOI: 10.1002/jcb.29035.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseGuinea pigsMammalian brainSporadic Creutzfeldt-Jakob diseaseOnly excitatory neuronsHippocampal pyramidal neuronsGranule cell layerInternal granule cell layerPancreatic islet cellsPyramidal neuronsSporadic CJDHidden infectionType synapsesExcitatory synapsesExcitatory neuronsMossy fibersPurkinje neuronsProgressive neurodegenerationNeuron synapsesIslet cellsSpecific neuronsWestern blotNeuronsPancreatic exocrine cellsKidney tubules
2018
Prokaryotic SPHINX 1.8 REP protein is tissue‐specific and expressed in human germline cells
Manuelidis L. Prokaryotic SPHINX 1.8 REP protein is tissue‐specific and expressed in human germline cells. Journal Of Cellular Biochemistry 2018, 120: 6198-6208. PMID: 30317668, DOI: 10.1002/jcb.27907.Peer-Reviewed Original ResearchConceptsOpen reading frameReplication initiation sequencesTissue-specific patternsHuman germline cellsSmall circular DNAREP peptidesGermline cellsMaternal inheritanceRep proteinSomatic cellsReading frameCell communicationEnvironmental infectious agentsMature spermDifferentiation functionPhage virusesCultured cellsCircular DNAInitiation sequenceSymbiotic elementsExocrine cellsFunctional differentiationSpinal cord synapsesMammalian brainDNA
2017
A prokaryotic viral sequence is expressed and conserved in mammalian brain
Yeh YH, Gunasekharan V, Manuelidis L. A prokaryotic viral sequence is expressed and conserved in mammalian brain. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7118-7123. PMID: 28630311, PMCID: PMC5502646, DOI: 10.1073/pnas.1706110114.Peer-Reviewed Original ResearchConceptsTissue-specific differentiationViral sequencesMammalian evolutionLimited proteinase K digestionMammalian sequencesHost prion proteinMaternal inheritanceProkaryotic virusesNeuronal cell lineDNA sequencesEssential functionsImperfect homologyEnvironmental microorganismsProteinase K digestionPhage virusesPrion proteinAmyloid formCytoplasmic particlesNeural cellsK digestionMammalian brainCell linesSPX1MammalsHomology
2016
CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection
Botsios S, Manuelidis L. CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection. Journal Of Cellular Biochemistry 2016, 117: 1947-1958. PMID: 26773845, DOI: 10.1002/jcb.25495.Peer-Reviewed Original ResearchConceptsTSE agentsTransmissible spongiform encephalopathiesAdaptive immune responsesDegenerative brain changesInfectious particlesHost prion proteinGT1 neuronal cellsForms of PrPLymphoreticular tissuesBrain changesImmune responseTSE strainsNeuronal cellsNeurodegenerative diseasesLatent virusInfectivity assaysSpongiform encephalopathiesNucleic acid genomeTitersEpidemic spreadViral structuresPrion proteinHost proteinsVirusHost components
2015
Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms
Botsios S, Tittman S, Manuelidis L. Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms. Virulence 2015, 6: 787-801. PMID: 26556670, PMCID: PMC4826107, DOI: 10.1080/21505594.2015.1098804.Peer-Reviewed Original ResearchConceptsInfectious titerInnate immune responseHuman CJDResistant virusesIatrogenic infectionGT1 cellsBrain changesImmune responseInfectious agentsTSE agentsScrapie agentCJDPrion protein amyloidSheep scrapieVirulent microbesInfectious particlesMin exposureIntrinsic resistanceTreatmentTitersPrP amyloidScrapieAmyloidCultured cellsDeep proteomic analysisProteomic analysis of host brain components that bind to infectious particles in Creutzfeldt‐Jakob disease
Kipkorir T, Colangelo CM, Manuelidis L. Proteomic analysis of host brain components that bind to infectious particles in Creutzfeldt‐Jakob disease. Proteomics 2015, 15: 2983-2998. PMID: 25930988, PMCID: PMC4601564, DOI: 10.1002/pmic.201500059.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseInfectious agentsTransmissible encephalopathiesNew therapeutic initiativesBrain particlesCausal infectious agentInfectious particlesHost prion proteinHost immune recognitionSynapsin-2Such therapyHost proteinsTherapeutic initiativesImmune recognitionStrain-specific patternsCommon pathwayCross-species transmissionHigh infectivityDiseaseViral pathwaysProteomic analysisHost targetsViral proteinsViral processingBrain components
2014
Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS
Kipkorir T, Tittman S, Botsios S, Manuelidis L. Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS. Journal Of Cellular Biochemistry 2014, 115: 2012-2021. PMID: 24933657, PMCID: PMC7166504, DOI: 10.1002/jcb.24873.Peer-Reviewed Original ResearchConceptsSporadic CJDMouse brainTransmissible encephalopathiesNormal human brain samplesHost prion proteinHuman brain samplesSCJD brainsPrion proteinAmyloid pathologyAPP processingNew therapiesUninfected controlsBrain homogenatesBrain samplesCellular findingsDetectable PrPNeurodegenerative diseasesSheep scrapieInfectious titerBrainProteinase KCJDLC-MS/MSViral motifsInfectious form
2012
Continuous Production of Prions after Infectious Particles Are Eliminated: Implications for Alzheimer’s Disease
Miyazawa K, Kipkorir T, Tittman S, Manuelidis L. Continuous Production of Prions after Infectious Particles Are Eliminated: Implications for Alzheimer’s Disease. PLOS ONE 2012, 7: e35471. PMID: 22509412, PMCID: PMC3324552, DOI: 10.1371/journal.pone.0035471.Peer-Reviewed Original Research
2011
High CJD infectivity remains after prion protein is destroyed
Miyazawa K, Emmerling K, Manuelidis L. High CJD infectivity remains after prion protein is destroyed. Journal Of Cellular Biochemistry 2011, 112: 3630-3637. PMID: 21793041, PMCID: PMC3202053, DOI: 10.1002/jcb.23286.Peer-Reviewed Original ResearchConceptsTransmissible spongiform encephalopathy agentsSpongiform encephalopathy agentInfectious particlesHost prion proteinPK digestionTotal PrPCJD infectivityInfectious homogenatesPrion proteinBrain resultsHigh titersTitersCell infectivityCell-based assaysCell culture assaysInfectivityProteinase K treatmentInfectious formPrPBrainCulture assaysAssaysProteinSensitive formK treatmentReplication and spread of CJD, kuru and scrapie agents in vivo and in cell culture
Miyazawa K, Emmerling K, Manuelidis L. Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture. Virulence 2011, 2: 188-199. PMID: 21527829, PMCID: PMC3149681, DOI: 10.4161/viru.2.3.15880.Peer-Reviewed Original ResearchConceptsGT1 cellsSporadic CJDTSE agentsScrapie agentAgent-specific patternsTransmissible spongiform encephalopathy agentsComplex innate immune responseSpongiform encephalopathy agentInnate immune responseHost prion proteinK scrapie agentHuman CJDCJD agentNeuropathological sequelaeBrain titersImmune responseHuman kuruClearance mechanismsCJDInhibitory effectEnvironmental agentsCell-based assaysKuruInfectious formDistinct incubation times
2010
Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD
Manuelidis L. Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD. Journal Of NeuroVirology 2010, 17: 131-145. PMID: 21165784, DOI: 10.1007/s13365-010-0007-0.Peer-Reviewed Original ResearchMeSH KeywordsAcinetobacterAmino Acid SequenceAnimalsBase SequenceBrainConserved SequenceCreutzfeldt-Jakob SyndromeCricetinaeDeoxyribonucleasesDNA HelicasesDNA, CircularDNA, MitochondrialDNA-Directed DNA PolymeraseElectrophoresis, Agar GelGenome, BacterialHumansMiceMolecular Sequence DataNeuroblastomaNeurodegenerative DiseasesPlasmidsPolymerase Chain ReactionPrionsScrapieTumor Cells, CulturedTransmissible encephalopathy agents
Manuelidis L. Transmissible encephalopathy agents. Virulence 2010, 1: 101-104. PMID: 21178425, PMCID: PMC3073180, DOI: 10.4161/viru.1.2.10822.Peer-Reviewed Original ResearchConceptsTransmissible spongiform encephalopathiesKuru agentNormal miceRecent transmissionInfectious agentsTissue pathologyTSE agentsDisease latencyVirulence characteristicsNeural cellsSpongiform encephalopathiesPrion hypothesisEpidemic spreadAgentsGeographic regionsEncephalopathyVirulenceSuperinfectionMicePathologyAgent-specific Shadoo Responses in Transmissible Encephalopathies
Miyazawa K, Manuelidis L. Agent-specific Shadoo Responses in Transmissible Encephalopathies. Journal Of Neuroimmune Pharmacology 2010, 5: 155-163. PMID: 20112073, PMCID: PMC2875883, DOI: 10.1007/s11481-010-9191-1.Peer-Reviewed Original ResearchConceptsAgent-specific differencesTransmissible spongiform encephalopathiesGT1 cellsTga20 miceTSE agentsHost prion proteinKuru agentRegional neuropathologyIntracellular amyloidSporadic CJDPrP changesTSE infectionUninfected controlsPrP levelsInfectious agentsAbnormal PrPTransmissible encephalopathiesMiceNeurodegenerative diseasesScrapie agentCJDInfectionInfected cellsSheep scrapieSpongiform encephalopathies
2009
The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents
Manuelidis L, Chakrabarty T, Miyazawa K, Nduom NA, Emmerling K. The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 13529-13534. PMID: 19633190, PMCID: PMC2715327, DOI: 10.1073/pnas.0905825106.Peer-Reviewed Original ResearchConceptsSporadic Creutzfeldt-Jakob diseaseCreutzfeldt-Jakob diseaseBovine spongiform encephalopathyBSE agentHuman sporadic Creutzfeldt-Jakob diseaseInfectious agentsEpidemic bovine spongiform encephalopathyTSE agentsScrapie agentTransmissible spongiform encephalopathy agentsSpongiform encephalopathy agentKuru agentLymphoreticular involvementBrain neuropathologySporadic CJDGT1 cellsNormal miceInfected humansNeurodegenerative diseasesDiseaseViral receptorsInfectious neurodegenerative diseasesSheep scrapieSpongiform encephalopathiesHigh levels
2001
Blood borne transit of CJD from brain to gut at early stages of infection
Radebold K, Chernyak M, Martin D, Manuelidis L. Blood borne transit of CJD from brain to gut at early stages of infection. BMC Infectious Diseases 2001, 1: 20. PMID: 11716790, PMCID: PMC59894, DOI: 10.1186/1471-2334-1-20.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseIC inoculationAbnormal PrPCJD agentTransmissible spongiform encephalopathiesLymphoreticular tissuesEnteric infectionsIp inoculationPrP accumulationSpinal cordPeripheral tissuesGastrointestinal tractInfectious inoculumLymphatic drainageInfectious agentsVascular routeCell infectivityInfectionTerminal stageDiseaseSpongiform encephalopathiesDifferent organsBrainDaysProgressive appearance
1985
Individual interphase chromosome domains revealed by in situ hybridization
Manuelidis L. Individual interphase chromosome domains revealed by in situ hybridization. Human Genetics 1985, 71: 288-293. PMID: 3908288, DOI: 10.1007/bf00388453.Peer-Reviewed Original ResearchConceptsInterphase chromosomesHuman chromosomesMouse-human cell hybridsCharacteristic folding patternSingle human chromosomeHuman interphase chromosomesSitu hybridizationHuman DNA probesInterphase chromosome domainsChromosome domainsIndividual chromosomesCell hybridsInterphase nucleiChromosomesDNA probesHybrid cellsFolding patternInterphase domainHybridizationOptical sectionsDomainNucleusWide fibersHybridization solutionReproducible position
1983
Scrapie-associated fibrils in Creutzfeldt–Jakob disease
Merz P, Somerville R, Wisniewski H, Manuelidis L, Manuelidis E. Scrapie-associated fibrils in Creutzfeldt–Jakob disease. Nature 1983, 306: 474-476. PMID: 6358899, DOI: 10.1038/306474a0.Peer-Reviewed Original ResearchConceptsScrapie associated fibrilsCreutzfeldt-Jakob diseaseCentral nervous systemTitre of infectivityScrapie of sheepInfected brainPathological responseProgressive degenerationNervous systemSynaptosomal preparationsInfectious agentsBrain fractionsTransmissible encephalopathiesDiseaseHuman casesSpleen extractsAbnormal fibrilsSusceptible hostsScrapieClose associationDifferent tissuesEncephalopathyAgentsDegenerationTitres