A disease specific structure termed scrapie associated fibril (SAF) has been observed by negative stain electron microscopy exclusively in the uncoventional slow virus diseases. SAF have been seen in naturally occurring or experimentally induced cases of Creutzfeldt-Jakob disease, Kuru, Scrapie, Gerstmann-Straussler syndrome and chronic wasting disease. These structures have not been found in a comprehensive series of controls sharing common histopathologies, ultrastructural features and disease symptoms. Evidence suggests SAF to be a component of the infectious agent or the agent itself. Purification of scrapie infectivity in the 263K hamster model has yielded SAF as the only ultrastructural entity; an indication of identity between agent and SAF. A scrapie agent strain specific polypeptide has been observed by polyacrylamide gel electrophoresis in purified preparations of SAF; 2lK for l39A scrapie agent, 22K for ME7 scrapie agent and 25K for 263K scrapie agent. The implication of these findings is that the scrapie agent imparts genetic control over the components of SAF by way of its own genetic information. The purification and molecular characterization of SAF represents a means to link scrapie infectivity with a morphologically identifiable structure, a unique polypeptide and potentially with a nucleic acid. Antibody probes and potential nucleic acid probes generated to SAF will permit studies on the replication and pathogenesis of these agents and provide a much needed diagnostic tool within the area of unconventional slow virus diseases. These probes provide the potential to investigate the role of similar agents in Senile Dementia of the Alzheimer Type and in other CNS disorders of unknown etiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021349-02
Application #
3402415
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Institute for Basic Research in Dev Disabil
Department
Type
DUNS #
167205090
City
Staten Island
State
NY
Country
United States
Zip Code
10314
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Carp, R I; Callahan, S M; Patrick, B A et al. (1994) Interaction of scrapie agent and cells of the lymphoreticular system. Arch Virol 136:255-68
Casaccia-Bonnefil, P; Kascsak, R J; Fersko, R et al. (1993) Brain regional distribution of prion protein PrP27-30 in mice stereotaxically microinjected with different strains of scrapie. J Infect Dis 167:7-12
Bendheim, P E; Brown, H R; Rudelli, R D et al. (1992) Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology 42:149-56
Wrzolek, M A; Merz, P A; Kascsak, R et al. (1992) Immune electron microscopic characterization of monoclonal antibodies to Alzheimer neurofibrillary tangles. Am J Pathol 141:343-55
Rubenstein, R; Merz, P A; Kascsak, R J et al. (1991) Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins. J Infect Dis 164:29-35
Kascsak, R J; Rubenstein, R; Carp, R I (1991) Evidence for biological and structural diversity among scrapie strains. Curr Top Microbiol Immunol 172:139-52
Rubenstein, R; Deng, H; Scalici, C L et al. (1991) Alterations in neurotransmitter-related enzyme activity in scrapie-infected PC12 cells. J Gen Virol 72 ( Pt 6):1279-85
Cashman, N R; Loertscher, R; Nalbantoglu, J et al. (1990) Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell 61:185-92
Kim, Y S; Carp, R I; Callahan, S et al. (1990) Incubation periods and histopathological changes in mice injected stereotaxically in different brain areas with the 87V scrapie strain. Acta Neuropathol 80:388-92

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