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.