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Asynchronous onset of clinical disease in BSE-infected macaques.

Montag J, Schulz-Schaeffer W, Schrod A, Hunsmann G, Motzkus D - Emerging Infect. Dis. (2013)

Bottom Line: To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques.The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.

View Article: PubMed Central - PubMed

Affiliation: German Primate Center, Göttingen, Germany.

ABSTRACT
To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.

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PrPSc profile of macaque-adapted BSE in comparison to human CJD. Brain homogenates from human sCJD type 1, sCJD type 2, vCJD, and BSE-infected macaques were subjected to PK treatment, separated on 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and blotted onto nitrocellulose membranes. A) PrPSc for human and macaque brain was detected with the widely used monoclonal antibody 3F4 or with 11C6. B) Glycoform ratio of sCJD type 2, vCJD, and macaque-adapted BSE. The relative signal intensities of the diglycosylated, monoglycosylated, and nongylcosylated isoforms were determined densitometrically and normalized to the band of the nongylcosylated isoform. PrPSc, prion protein isoform; BSE, bovine spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; vCJD, variant CJD; PK, proteinase K.
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Figure 2: PrPSc profile of macaque-adapted BSE in comparison to human CJD. Brain homogenates from human sCJD type 1, sCJD type 2, vCJD, and BSE-infected macaques were subjected to PK treatment, separated on 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and blotted onto nitrocellulose membranes. A) PrPSc for human and macaque brain was detected with the widely used monoclonal antibody 3F4 or with 11C6. B) Glycoform ratio of sCJD type 2, vCJD, and macaque-adapted BSE. The relative signal intensities of the diglycosylated, monoglycosylated, and nongylcosylated isoforms were determined densitometrically and normalized to the band of the nongylcosylated isoform. PrPSc, prion protein isoform; BSE, bovine spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; vCJD, variant CJD; PK, proteinase K.

Mentions: The individual glycopattern and band migration of macaque-adapted PrPSc was compared with human sporadic CJD (sCJD) type 1, sCJD type 2, and vCJD. PK-resistant PrP from BSE-infected macaques co-migrated with type 2 sCJD and was clearly distinguishable from type 1 sCJD (Figure 2). The glycosylation pattern of macaque-adapted BSE was comparable with vCJD (6,7), which is characterized by an overrepresentation of diglycosylated PrPSc (8,9). Using 11C6 antibody (10), we detected a slightly decreased signal of the diglycosylated PrPSc isoform for sCJD, vCJD, and macaque-adapted BSE. We assume that this effect is related to a reduced affinity of the diglycosylated isoform to 11C6 that otherwise shows high sensitivity to macaque-adapted PrPSc. Nevertheless, direct comparison showed a higher amount of the diglysosylated PrPSc isoform in vCJD and macaque-adapted BSE than sCJD, which was also shown with a different monoclonal antibody, 3F4. This finding confirms that BSE transmission to macaques is comparable with, and can be used as a model for, human vCJD infection.


Asynchronous onset of clinical disease in BSE-infected macaques.

Montag J, Schulz-Schaeffer W, Schrod A, Hunsmann G, Motzkus D - Emerging Infect. Dis. (2013)

PrPSc profile of macaque-adapted BSE in comparison to human CJD. Brain homogenates from human sCJD type 1, sCJD type 2, vCJD, and BSE-infected macaques were subjected to PK treatment, separated on 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and blotted onto nitrocellulose membranes. A) PrPSc for human and macaque brain was detected with the widely used monoclonal antibody 3F4 or with 11C6. B) Glycoform ratio of sCJD type 2, vCJD, and macaque-adapted BSE. The relative signal intensities of the diglycosylated, monoglycosylated, and nongylcosylated isoforms were determined densitometrically and normalized to the band of the nongylcosylated isoform. PrPSc, prion protein isoform; BSE, bovine spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; vCJD, variant CJD; PK, proteinase K.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3713963&req=5

Figure 2: PrPSc profile of macaque-adapted BSE in comparison to human CJD. Brain homogenates from human sCJD type 1, sCJD type 2, vCJD, and BSE-infected macaques were subjected to PK treatment, separated on 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and blotted onto nitrocellulose membranes. A) PrPSc for human and macaque brain was detected with the widely used monoclonal antibody 3F4 or with 11C6. B) Glycoform ratio of sCJD type 2, vCJD, and macaque-adapted BSE. The relative signal intensities of the diglycosylated, monoglycosylated, and nongylcosylated isoforms were determined densitometrically and normalized to the band of the nongylcosylated isoform. PrPSc, prion protein isoform; BSE, bovine spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; vCJD, variant CJD; PK, proteinase K.
Mentions: The individual glycopattern and band migration of macaque-adapted PrPSc was compared with human sporadic CJD (sCJD) type 1, sCJD type 2, and vCJD. PK-resistant PrP from BSE-infected macaques co-migrated with type 2 sCJD and was clearly distinguishable from type 1 sCJD (Figure 2). The glycosylation pattern of macaque-adapted BSE was comparable with vCJD (6,7), which is characterized by an overrepresentation of diglycosylated PrPSc (8,9). Using 11C6 antibody (10), we detected a slightly decreased signal of the diglycosylated PrPSc isoform for sCJD, vCJD, and macaque-adapted BSE. We assume that this effect is related to a reduced affinity of the diglycosylated isoform to 11C6 that otherwise shows high sensitivity to macaque-adapted PrPSc. Nevertheless, direct comparison showed a higher amount of the diglysosylated PrPSc isoform in vCJD and macaque-adapted BSE than sCJD, which was also shown with a different monoclonal antibody, 3F4. This finding confirms that BSE transmission to macaques is comparable with, and can be used as a model for, human vCJD infection.

Bottom Line: To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques.The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.

View Article: PubMed Central - PubMed

Affiliation: German Primate Center, Göttingen, Germany.

ABSTRACT
To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.

Show MeSH
Related in: MedlinePlus