1. Blood clearance of the prion protein introduced by intravenous route in sheep is influenced by host genetic and physiopathologic factors
- Author
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Véronique Gayrard, Elisabeth C Jeunesse, Human Rezaei, Guillaume Tabouret, Catherine Viguié, Pierre-Louis Toutain, Nicole Picard-Hagen, Physiopathologie et Toxicologie Expérimentales (UPTE), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), and Institut National de la Recherche Agronomique (INRA)
- Subjects
Gene isoform ,medicine.medical_specialty ,Blood transfusion ,Genotype ,Prions ,[SDV]Life Sciences [q-bio] ,animal diseases ,medicine.medical_treatment ,Immunology ,030204 cardiovascular system & hematology ,Biology ,Nephrectomy ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Internal medicine ,medicine ,Animals ,Immunology and Allergy ,Prion protein ,Host genotype ,030304 developmental biology ,Immunoassay ,0303 health sciences ,Sheep ,Transmissible spongiform encephalopathy ,Hematology ,medicine.disease ,Virology ,Recombinant Proteins ,nervous system diseases ,Kinetics ,Endocrinology ,Injections, Intravenous ,Recombinant DNA ,Blood clearance ,Intravenous route ,Scrapie - Abstract
International audience; BACKGROUND: The risk of transmissible spongiform encephalopathy (TSE) transmission by blood transfusion is dependent on the blood concentrations of the pathologic isoform of prion protein (PrPsc) but may also be influenced by blood concentrations of cellular PrP (PrPc). These concentrations are controlled by the blood clearance of PrP, which has never been evaluated. STUDY DESIGN AND METHODS: The blood (actually plasma) clearance of ovine purified prokaryote recombinant PrP (rPrP) was measured in genotyped and in nephrectomized sheep. The exposure to proteinase Kresistant fragments of PrP (PrPres) after intravenous (IV) administration of scrapie-associated fibrils (SAFs) was also investigated in a sheep. RESULTS: The ARR variant of rPrP was eliminated more rapidly than its VRQ counterpart. The PrPc plasma concentrations in homozygous highly susceptible VRQ sheep were greater than in homozygous ARR-resistant sheep, suggesting that clearance of the ARR variant of PrPc was higher than that of the VRQ variant. The plasma clearance of rPrP was decreased by 52 percent after a bilateral nephrectomy indicating the significant contribution of the kidneys in eliminating rPrP. PrPres was shown to be slowly eliminated after IV administration of scrapie-associated fibrils. CONCLUSION: PrP host genotype and physiopathologic factors could influence the risk of TSE transmission by modulating blood PrP clearance. This risk was increased by the sustained exposure to PrPres after IV administration. It should be noted that although the materials that have been administered (rPrP and SAFs) were not the actual species of interest, they can be of value as probes for investigating PrP clearance mechanisms.
- Published
- 2008