학술논문
Glycans are not necessary to maintain the pathobiological features of bovine spongiform encephalopathy
Research Article
Research Article
Document Type
Report
Author
Source
PLoS Pathogens. October 7, 2022, Vol. 18 Issue 10, e1010900
Subject
Language
English
ISSN
1553-7366
Abstract
Author(s): Alicia Otero 1, Tomás Barrio 2, Hasier Eraña 3,4, Jorge M. Charco 3,4, Marina Betancor 1, Carlos M. Díaz-Domínguez 3, Belén Marín 1, Olivier Andréoletti 2, Juan M. Torres [...]
The role of the glycosylation status of PrP.sup.C in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrP.sup.C . Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrP.sup.C -expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrP.sup.C is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties.
The role of the glycosylation status of PrP.sup.C in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrP.sup.C . Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrP.sup.C -expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrP.sup.C is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties.