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Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion


The transmissible spongiform encephalopathies (TSEs) are a group of infectious neurodegenerative diseases affecting both humans and animals. The prion hypothesis postulates that prions are protein conformation based infectious agents responsible for TSE infectivity. Prions have been synthetically generated in vitro, but it remains unclear whether the properties of synthetically generated prion are the same as those of TSE agents and whether the disease caused by synthetically generated prion is identical to naturally occurring TSEs. In this study, we demonstrated that similar to the classical TSE agents, the synthetically generated prion has a titratable infectivity and is able to cause prion disease in wild-type mice via routes other than direct intra-cerebral inoculation. More importantly, we showed that the synthetically generated prion induced pathological changes, including the dissemination of disease-specific prion protein accumulation and the route and mechanism of neuroinvasion, were all typical of classical TSEs. These results demonstrate the similarity of synthetically generated prion to the infectious agent in TSEs, providing strong evidence supporting the prion hypothesis.


Vyšlo v časopise: Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004958
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004958

Souhrn

The transmissible spongiform encephalopathies (TSEs) are a group of infectious neurodegenerative diseases affecting both humans and animals. The prion hypothesis postulates that prions are protein conformation based infectious agents responsible for TSE infectivity. Prions have been synthetically generated in vitro, but it remains unclear whether the properties of synthetically generated prion are the same as those of TSE agents and whether the disease caused by synthetically generated prion is identical to naturally occurring TSEs. In this study, we demonstrated that similar to the classical TSE agents, the synthetically generated prion has a titratable infectivity and is able to cause prion disease in wild-type mice via routes other than direct intra-cerebral inoculation. More importantly, we showed that the synthetically generated prion induced pathological changes, including the dissemination of disease-specific prion protein accumulation and the route and mechanism of neuroinvasion, were all typical of classical TSEs. These results demonstrate the similarity of synthetically generated prion to the infectious agent in TSEs, providing strong evidence supporting the prion hypothesis.


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