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Agents that cause transmissible subacute spongiform encephalopathies.
1CEA, Service de Neurovirologie, DSV/DRM, Centre de Recherches du Service de Santé des Armées, Fontenay-aux-Roses, France.
Summary
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases. The prion hypothesis suggests the prion protein (PrP) causes TSEs, but this remains unproven despite supporting data.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Transmissible spongiform encephalopathies (TSEs) are characterized by long incubation periods and central nervous system (CNS) degeneration.
- The exact nature of the causative agents, transmissible spongiform encephalopathy agents (TSA)/prions, is unknown.
- The prion hypothesis posits that host-derived prion proteins (PrP) are the transmissible agents, accumulating in infected individuals.
Purpose of the Study:
- To review the evidence supporting the prion hypothesis for TSEs.
- To discuss the characteristics of TSA/prions, including their replication, infectivity, and resistance to inactivation.
- To examine the distribution of infectivity in vivo and in vitro.
Main Methods:
- Review of existing experimental data on TSEs and prions.
- Analysis of PrP accumulation and resistance to proteinase K (PrP-res) in infected individuals.
- Evaluation of in vitro replication rates and susceptibility of cell types.
- Assessment of TSA/prion resistance to chemical and physical inactivation methods.
- Examination of in vivo infectivity distribution based on strain, host, and route of inoculation.
Main Results:
- PrP accumulation correlates with infectivity titres and PrP-res is resistant to proteinase K.
- Iatrogenic Creutzfeldt-Jakob disease (CJD) cases highlight human transmission risks via medical procedures.
- The CNS exhibits the highest infectivity rate, though infectivity varies by organ.
- In vitro, TSA/prions replicate slowly, primarily in neuronal cells.
- TSA/prions exhibit resistance to conventional viral inactivation methods, requiring specific high-temperature autoclaving or chemical treatments for inactivation.
Conclusions:
- Strong experimental evidence supports the prion hypothesis, but it is not yet definitively proven.
- TSA/prions possess unique properties, including resistance to inactivation, necessitating stringent public health measures.
- Understanding prion infectivity and distribution is crucial for preventing iatrogenic transmission and managing TSEs.