Dataset Information

Protective Effect of Val₁₂₉-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

ABSTRACT: Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met₁₂₉) or valine (Val₁₂₉) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met₁₂₉ homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val₁₂₉ Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met₁₂₉ Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val₁₂₉ Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val₁₂₉ Hu-PrP-positive humans with the emergence of new strain features.

SUBMITTER: Fernandez-Borges N

PROVIDER: S-EPMC5572891 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Fernández-Borges Natalia N Espinosa Juan Carlos JC Marín-Moreno Alba A Aguilar-Calvo Patricia P Asante Emmanuel A EA Kitamoto Tetsuyuki T Mohri Shirou S Andréoletti Olivier O Torres Juan María JM

Emerging infectious diseases 20170901 9

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heteroz ...[more]

PMID: 28820136

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Project description:The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrPSc, were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates.ImportanceVariant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for propagating BSE and vCJD prions.

Dataset Information

Protective Effect of Val₁₂₉-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Publications

Protective Effect of Val<sub>129</sub>-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

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Dataset Information

Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Publications

Protective Effect of Val&lt;sub&gt;129&lt;/sub&gt;-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Protective Effect of Val₁₂₉-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Protective Effect of Val<sub>129</sub>-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.