title: First demonstration of transmissible spongiform encephalopathy-associated prion protein (PrPTSE) in extracellular vesicles from plasma of mice infected with mouse-adapted variant Creutzfeldt-Jakob disease by in vitro amplification.
abstract: The development of variant Creutzfeldt-Jakob disease (vCJD) in three recipients of non-leukoreduced red blood cells from asymptomatic donors who subsequently developed the disease has confirmed existing concerns about the possible spread of transmissible spongiform encephalopathies (TSEs) via blood products. In addition, the presence of disease-associated misfolded prion protein (PrP(TSE)), generally associated with infectivity, has been demonstrated in the blood of vCJD patients. However, its origin and distribution in this biological fluid are still unknown. Various studies have identified cellular prion protein (PrP(C)) among the protein cargo in human blood-circulating extracellular vesicles released from endothelial cells and platelets, and exosomes isolated from the conditioned media of TSE-infected cells have caused the disease when injected into experimental mice. In this study, we demonstrate the detection of PrP(TSE) in extracellular vesicles isolated from plasma samples collected during the preclinical and clinical phases of the disease from mice infected with mouse-adapted vCJD and confirm the presence of the exosomal marker Hsp70 in these preparations.
authors.affiliation: From the Transmissible Diseases Department, Biomedical Services Holland Laboratory, American National Red Cross, Rockville, Maryland 20855 and Paula.Saa@redcross.org.
authors.forename: Paula
authors.initials: P
authors.lastname: Saá
authors.affiliation: From the Transmissible Diseases Department, Biomedical Services Holland Laboratory, American National Red Cross, Rockville, Maryland 20855 and.
authors.forename: Oksana
authors.initials: O
authors.lastname: Yakovleva
authors.affiliation: From the Transmissible Diseases Department, Biomedical Services Holland Laboratory, American National Red Cross, Rockville, Maryland 20855 and.
authors.forename: Jorge
authors.initials: J
authors.lastname: de Castro
authors.affiliation: From the Transmissible Diseases Department, Biomedical Services Holland Laboratory, American National Red Cross, Rockville, Maryland 20855 and.
authors.forename: Irina
authors.initials: I
authors.lastname: Vasilyeva
authors.affiliation: the Laboratory of Cellular Hematology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Silvia H
authors.initials: SH
authors.lastname: De Paoli
authors.affiliation: the Laboratory of Cellular Hematology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Jan
authors.initials: J
authors.lastname: Simak
authors.affiliation: From the Transmissible Diseases Department, Biomedical Services Holland Laboratory, American National Red Cross, Rockville, Maryland 20855 and.
authors.forename: Larisa
authors.initials: L
authors.lastname: Cervenakova
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002478:Cells, Cultured; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D019286:Endopeptidase K / Q000737:chemistry; D055354:Exosomes / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D011489:Protein Denaturation; D017510:Protein Folding
chemical_list: D017077:Culture Media, Conditioned; D018840:HSP70 Heat-Shock Proteins; D007074:Immunoglobulin G; D011328:Prions; D019286:Endopeptidase K; D000432:Methanol
keywords: Blood; Cell Culture; Exosome; Extracellular Vesicles; Mouse