All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

Abstract

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.

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

“…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).…”

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

“…In this context, the PrP transgenic Drosophila model we describe here could be considered to be of comparable, if not greater, sensitivity than transfusion studies in the natural host since plasma from scrapie-affected sheep is reported to contain less prion infectivity than whole blood [19]. In addition, the length of time required to bioassay plasma in PrP transgenic Drosophila was considerably less than that required by transfusion studies in the natural host [23].…”

“…Studies in ruminants have analysed bioassays of autologous whole or fractionated blood by the intravenous route [19,20]. These experimental transfusion studies have confirmed that all blood fractions prepared by protocols similar to those used in transfusion medicine can transmit prion disease [23,24]. In addition, prion transmission by transfusion of cellular blood fractions was not solely dependent on their infectious titre since prion disease was more efficiently transmitted with viable rather than non-viable leukocytes [20].…”

El silenciamiento de la proteína priónica celular (PrPC) mediante RNA de interferencia (siRNA) reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

“…El hecho de que la PrP C se exprese en células sanguíneas del tipo monocito macrófago, podría representar un importante blanco para bloquear la replicación y la transmisión de la PrP Sc . Se han reportado evidencias de la posible transmisión de PrP Sc por sangre (23)(24)(25) , por lo tanto el silenciamiento de PrP C en el flujo sanguíneo podría reducir el nivel de infección o su rapidez de diseminación hacia el SNC.…”

“…The fact that PrP C is expressed in blood monocytes and macrophages, these cells could represent an important target for blocking PrP Sc replication and transmission. Evidences of possible PrP Sc transmission via blood have been reported (23)(24)(25) ; therefore, PrP C silencing in blood flow could decrease the level of infection or its speed to spread towards the CNS.…”