title: Are prions transported by plasma exosomes?
abstract: Blood has been shown to contain disease-associated misfolded prion protein (PrP(TSE)) in animals naturally and experimentally infected with various transmissible spongiform encephalopathy (TSE) agents, and in humans infected with variant Creutzfeldt-Jakob disease (vCJD). Recently, we have demonstrated PrP(TSE) in extracellular vesicle preparations (EVs) containing exosomes from plasma of mice infected with mouse-adapted vCJD by Protein Misfolding Cyclic Amplification (PMCA). Here we report the detection of PrP(TSE) by PMCA in EVs from plasma of mice infected with Fukuoka-1 (FU), an isolate from a Gerstmann-Sträussler-Scheinker disease patient. We used Tga20 transgenic mice that over-express mouse cellular prion protein, to assay by intracranial injections the level of infectivity in a FU-infected brain homogenate from wild-type mice (FU-BH), and in blood cellular components (BCC), consisting of red blood cells, white blood cells and platelets, plasma EVs, and plasma EVs subjected to multiple rounds of PMCA. Only FU-BH and plasma EVs from FU-infected mice subjected to PMCA that contained PrP(TSE) transmitted disease to Tga20 mice. Plasma EVs not subjected to PMCA and BCC from FU-infected mice failed to transmit disease. These findings confirm the high sensitivity of PMCA for PrP(TSE) detection in plasma EVs and the efficiency of this in vitro method to produce highly infectious prions. The results of our study encourage further research to define the role of EVs and, more specifically exosomes, as blood-borne carriers of PrP(TSE).
authors: Scientific Affairs, American National Red Cross, Rockville, Maryland, USA. Electronic address: larisa.cervenakova@redcross.org.
authors: Larisa
authors: L
authors: Cervenakova
authors: Scientific Affairs, American National Red Cross, Rockville, Maryland, USA.
authors: Paula
authors: P
authors: Saá
authors: Scientific Affairs, American National Red Cross, Rockville, Maryland, USA; The Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, DETTD, OBRR, CBER, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
authors: Oksana
authors: O
authors: Yakovleva
authors: Scientific Affairs, American National Red Cross, Rockville, Maryland, USA.
authors: Irina
authors: I
authors: Vasilyeva
authors: Scientific Affairs, American National Red Cross, Rockville, Maryland, USA; Meso Scale Diagnostics, LLC, Rockville, Maryland, USA.
authors: Jorge
authors: J
authors: de Castro
authors: National Institutes of Health, Bethesda, Maryland, USA.
authors: Paul
authors: P
authors: Brown
authors: Scientific Affairs, American National Red Cross, Rockville, Maryland, USA.
authors: Roger
authors: R
authors: Dodd
mesh_terms: D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood / Q000235:genetics; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D016098:Gerstmann-Straussler-Scheinker Disease / Q000097:blood* / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000097:blood* / Q000235:genetics; D021381:Protein Transport / Q000235:genetics
chemical_list: D011328:Prions
keywords: Blood; Extracellular vesicles; Plasma; Prion infectivity; Prion protein