The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy

Brown, Paul; Rohwer, Robert G.; Dunstan, B C; MacAuley, Claudia; Gajdusek, D. Carleton; Drohan, William N.

doi:10.1046/j.1537-2995.1998.38998408999.x

Cited by 284 publications

(261 citation statements)

References 17 publications

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“…Our studies here support the view that the level of prion infectivity in blood from prion-diseased individuals may be underestimated when assessed by intracerebral inoculation of rodents in comparison with bioassay of similar material in other experimental systems. This is particularly pertinent to our assessment here of prion-infected plasma that could be diluted by several orders of magnitude and still trigger a phenotypic response in the PrP transgenic Drosophila, but appears to contain a low level of infectivity when assayed in other systems [10,[15][16][17][18][19][20][21]. One possibility for the efficient detection of scrapie-infected sheep plasma by PrP transgenic Drosophila is that this invertebrate host does not normally express PrP and may therefore not have evolved suitable defence mechanisms that efficiently remove or sequester misfolded neurotoxic forms of this protein.…”

Section: Discussionmentioning

confidence: 99%

“…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]. Studies in ruminants have analysed bioassays of autologous whole or fractionated blood by the intravenous route [19,20].…”

Section: Introductionmentioning

confidence: 93%

“…The occurrence of vCJD prions in human lymphoid tissue, together with the detection of prion infectivity in the blood of animals with asymptomatic experimental prion disease [10,11], raised the possibility for the potential of blood-borne vCJD transmission. These concerns were realised with the emergence of cases of vCJD in individuals within the U.K. who had received red blood cell concentrates [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…The bioassay of blood-borne prion infectivity has been performed for a variety of different species, such as rodents, sheep, cervids and primates including humans, undergoing, collectively, either experimental or natural prion disease [10,[15][16][17][18][19][20][21]. 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.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Thackray

Andréoletti

Bujdoso

2016

Biochemical Journal

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“…In an attempt to establish the distribution of infectivity in blood, normal human blood was spiked with scrapie-infected hamster brain homogenate [38]. This showed that the highest concentration of infectivity was in the cellular blood components, with lower levels in plasma, cryoprecipitate and Cohn fractions I-III, with almost none detected in fractions IV and V [38].…”

Section: Evidence For Infectivity In Blood In Prion Diseasesmentioning

confidence: 99%

Variant Creutzfeldt–Jakob disease and its transmission by blood

Ironside

Head

2003

Journal of Thrombosis and Haemostasis

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Summary. Variant Creutzfeldt–Jakob disease (vCJD) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (BSE). vCJD differs from all other human prion diseases in that the disease‐associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell‐associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease‐associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease‐associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD.

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Risk of Transmission of Bovine Spongiform Encephalopathy to Humans in the United States<SUBTITLE>Report of the Council on Scientific Affairs</SUBTITLE>

Tan¹

1999

JAMA

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Current risk of transmission of BSE in the United States is minimal because (1) BSE has not been shown to exist in this country; (2) adequate regulations exist to prevent entry of foreign sources of BSE into the United States; (3) adequate regulations exist to prevent undetected cases of BSE from uncontrolled amplification within the US cattle population; and (4) adequate preventive guidelines exist to prevent high-risk bovine materials from contaminating products intended for human consumption.

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The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy

Cited by 284 publications

References 17 publications

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Variant Creutzfeldt–Jakob disease and its transmission by blood

Risk of Transmission of Bovine Spongiform Encephalopathy to Humans in the United States<SUBTITLE>Report of the Council on Scientific Affairs</SUBTITLE>

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