Related Experiment Videos
The nature of the unconventional slow infection agents remains a puzzle
Abstract:
Unconventional slow infections are progressive transmissible degenerative disorders of the central nervous system. The human diseases belonging to this group are Creutzfeld-Jakob disease, kuru, and Gerstmann-Straussler syndrome. Scrapie, transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, and the recently discovered bovine spongiform encephalopathy are similar diseases found in animals. Unusual characteristics of the unconventional slow infections clearly distinguish these disorders from conventional infections. These include: unusually long incubation periods (from months to years); progressive CNS degeneration with characteristic histopathological lesions; the lack of an immune or inflammatory response; unconventional biological and physical properties of the etiologic agents. There has been considerable controversy concerning the nature of the causative agent. The 3 main hypotheses, virus, virino, and modified host protein, are reviewed relative to their ability to explain the properties of the agent and the unusual characteristics of the disease process. The discovery of an abnormal structure, termed scrapie associated fibrils (SAF) and an abnormally modified 33-37 kDa host-encoded glycoprotein unique to unconventional slow infections opened new areas of intense interest and investigation. SAF are abnormal filamentous structures which copurify with infectivity and possess characteristics of "amyloids." The major component of SAF is the host-encoded scrapie-specific protease resistant glyco-protein. Considerable data has accumulated on the biochemistry, immunology and molecular biology of this host coded scrapie protein. The relationship of SAF and the scrapie-specific protein to the infectious agent is discussed in the context of each of the "nature of the agent" hypotheses.
Insights
Unconventional slow infections, like Creutzfeldt-Jakob disease, are transmissible neurodegenerative disorders. Research explores the nature of their causative agents, focusing on scrapie-associated fibrils and a specific host protein.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Unconventional slow infections are progressive, transmissible, degenerative disorders of the central nervous system (CNS).
- Human diseases include Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler syndrome; animal diseases include scrapie and bovine spongiform encephalopathy.
- These infections exhibit long incubation periods, CNS degeneration, lack of immune response, and unusual agent properties.
Purpose of the Study:
- To review the main hypotheses regarding the nature of the causative agent of unconventional slow infections: virus, virino, and modified host protein.
- To discuss the discovery and characteristics of scrapie-associated fibrils (SAF) and a host-encoded glycoprotein.
- To analyze the relationship between SAF, the specific protein, and the infectious agent in the context of existing hypotheses.
Main Methods:
- Literature review of existing hypotheses on the nature of unconventional slow infection agents.
- Examination of the properties of scrapie-associated fibrils (SAF) and the related host-encoded glycoprotein.
- Comparative analysis of how different hypotheses explain the observed disease characteristics and agent properties.
Main Results:
- Scrapie-associated fibrils (SAF) are abnormal filamentous structures that copurify with infectivity and exhibit amyloid-like properties.
- The major component of SAF is a host-encoded, scrapie-specific, protease-resistant glycoprotein.
- Extensive data exists on the biochemistry, immunology, and molecular biology of this host-coded scrapie protein.
Conclusions:
- The discovery of SAF and the specific host protein provides new avenues for investigating unconventional slow infections.
- The properties of SAF and the scrapie protein are central to understanding the infectious agent's nature.
- Further research is needed to definitively establish the relationship between these structures and the infectious agent, informing the "nature of the agent" hypotheses.