Similar levels of infectivity in the blood of mice infected with human‐derived vCJD and GSS strains of transmissible spongiform encephalopathy

Červen̆áková, Larisa; Yakovleva, Oksana; McKenzie, Carroll; Kolchinsky, Svetlana; McShane, Lisa M.; Drohan, William N.; Brown, Paul

doi:10.1046/j.0041-1132.2003.00586.x

Cited by 142 publications

(140 citation statements)

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“…Multiple studies showed that TSE infectivity is present in the blood of experimental rodents, sheep with natural and experimental scrapie and experimental BSE, and deer affected with chronic wasting disease (CWD) (15)(16)(17)(18)(19)(20). PrP TSE has been successfully detected in the following: in whole blood of experimentally infected mice and hamsters, in sheep with natural scrapie and experimental BSE, and in white-tailed deer afflicted with CWD (21)(22)(23); in buffy coats of hamsters and sheep experimentally infected with scrapie (24 -26), as well as in plasma of mice and hamsters with scrapie; and in sheep and white-tailed deer naturally and experimentally infected with scrapie and CWD, respectively (27)(28)(29)(30).…”

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confidence: 99%

“…Detection of PrP TSE in EVs obtained from blood or other body fluids (urine, saliva, nasal secretions, and tears) will enable the design of minimally invasive or noninvasive diagnostic tests for TSEs. In this study, EVs, containing exosomes, were isolated from the conditioned media of cell cultures infected with mouse-adapted vCJD (Mo-vCJD) (16) or Fukuoka-1, a mouseadapted isolate from a Gerstmann-Sträussler-Scheinker disease patient (62,63), and from plasma collected periodically during the preclinical and clinical phases from Mo-vCJD-infected mice. They were used to seed serial automated protein misfolding cyclic amplification (saPMCA) reactions followed by PrP TSE detection by Western blotting.…”

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confidence: 99%

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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

Saá

Yakovleva

Castro

et al. 2014

Journal of Biological Chemistry

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Background: Prions can be transmitted by blood transfusion, but their origin and distribution in blood are unknown. Results: Prions were detected in plasma extracellular vesicles from preclinical and clinically sick mice. Conclusion: Prions associate with blood-circulating extracellular vesicles. Significance: These findings provide information about prion distribution in blood and set the groundwork for novel prion removal and disease diagnosis technologies.

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confidence: 99%

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confidence: 99%

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

Saá

Yakovleva

Castro

et al. 2014

Journal of Biological Chemistry

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“…Three human-to-human transmissions of variant Creutzfeldt-Jakob disease were reported in the United Kingdom in the past two years [1][2][3] . TSE infectivity in blood was also demonstrated in natural and experimental animal models such hamster 4,5 , mouse 6 , and sheep 7 . This funding has supported the development of a prototype assay for TSE infection using hamsters infected with the 263K stain of scrapie.…”

Section: Introductionmentioning

confidence: 85%

Development of an Assay for the Detection of PrPres in Blood and Urine Based on PMCA Assay and ELISA Methods

Rohwer¹,

Gregori²

2008

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe focus of this program is the development of a pre-clinical blood-based TSE diagnostic. The assay is been developed with plasma from hamsters infected with the 263K strain of scrapie. The assay has shown high sensitivity and specificity and good reproducibility. In this funding period we addressed two critical issues: Proteinase K (PK) digestion to discriminate PrPc, the normal form of the protein and PrPres the infection-specific form of the protein and denaturation of PrPres in plasma. The first issue was partially resolved when we discovered that PK digestion of plasma PrPc can be conducted without addition of SDS. We can now titer plasma and determine which PK condition is appropriate to digests all PrPc and no infectivity. We also identified the condition for plasma PrPres denaturation. We are currently developing the reagents and protocols for a "proof of principle" titration in plasma after PK digestion. This is the last step in the development of a complete plasma diagnostic assay. In a large, long term, "limiting dilution" titration of untreated, whole urine from scrapie infected hamsters, we have now conclusively shown that urine from TSE infected animals contains significant levels of infectivity and we will have a precise titer in another 6 months. Urine could thereby be an alternative substrate for disease detection. Bladder and kidney are also infectious.

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“…These bioassays have typically involved intracerebral inoculation of blood, or blood fractions, into a recipient indicator species, usually rodents including mice with a PrP transgene autologous for the donor species. Collectively, these studies revealed that prion infectivity titres of blood samples harvested during the asymptomatic phase of prion disease were up to 10-fold less than those collected during the clinical phase [10,19,20,22]. Infectious prions were found to be associated with white and red blood cells, platelets and plasma, although interspecies variations existed with regard to the distribution of prion infectivity in these different blood fractions [10,[15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 95%

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Thackray

Andréoletti

Bujdoso

2016

Biochemical Journal

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In pursuit of a tractable bioassay to assess blood prion infectivity, we have generated prion protein (PrP) transgenic Drosophila, which show a neurotoxic phenotype in adulthood after exposure to exogenous prions at the larval stage. Here, we determined the sensitivity of ovine PrP transgenic Drosophila to ovine prion infectivity by exposure of these flies to a dilution series of scrapie-infected sheep brain homogenate. Ovine PrP transgenic Drosophila showed a significant neurotoxic response to dilutions of 10−2 to 10−10 of the original scrapie-infected sheep brain homogenate. Significantly, we determined that this prion-induced neurotoxic response in ovine PrP transgenic Drosophila was transmissible to ovine PrP transgenic mice, which is indicative of authentic mammalian prion detection by these flies. As a consequence, we considered that PrP transgenic Drosophila were sufficiently sensitive to exogenous mammalian prions to be capable of detecting prion infectivity in the blood of scrapie-infected sheep. To test this hypothesis, we exposed ovine PrP transgenic Drosophila to scrapie-infected plasma, a blood fraction notoriously difficult to assess by conventional prion bioassays. Notably, pre-clinical plasma from scrapie-infected sheep induced neurotoxicity in PrP transgenic Drosophila and this effect was more pronounced after exposure to samples collected at the clinical phase of disease. The neurotoxic phenotype in ovine PrP transgenic Drosophila induced by plasma from scrapie-infected sheep was transmissible since head homogenate from these flies caused neurotoxicity in recipient flies during fly-to-fly transmission. Our data show that PrP transgenic Drosophila can be used successfully to bioassay prion infectivity in blood from a prion-diseased mammalian host.

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Similar levels of infectivity in the blood of mice infected with human‐derived vCJD and GSS strains of transmissible spongiform encephalopathy

Cited by 142 publications

References 26 publications

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

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

Development of an Assay for the Detection of PrPres in Blood and Urine Based on PMCA Assay and ELISA Methods

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

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