Specific Proteins Associated with Creutzfeldt--Jakob Disease and Scrapie Share Antigenic and Carbohydrate Determinants

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 12; pp. 4263 - 4267
• Main Authors: Manuelidis, Laura, Valley, Susan, Manuelidis, Elias E.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.06.1985; National Acad Sciences
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Antibodies; Biological and medical sciences; Brain Chemistry; Carbohydrate Sequence; Cell membranes; Creutzfeldt Jakob syndrome; Creutzfeldt-Jakob Syndrome - metabolism; Cricetinae; Detergents; Epitopes; Fundamental and applied biological sciences. Psychology; Gels; Glycoproteins; Glycoproteins - analysis; Glycoproteins - immunology; Guinea Pigs; Hamsters; Humans; Lectins; Microscopy, Electron; Molecular Weight; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - immunology; Nervous system diseases; Proteins; Scrapie - immunology; Scrapie - metabolism; Sheep; Solar fibrils; Solubility; Human; Antigenic determinant; Scrapie; Brain(Invertebrata); Glycoproteins; Identification; Experimental animal; Infection; Virus; Common antigen; Proteins; Specificity; Antigenicity; Viral disease; Creutzfeldt Jakob disease; Slow virus
• DOI: 10.1073/pnas.82.12.4263
• ISSN: 0027-8424

Small amounts of brain tissue (2 g) infected with Creutzfeldt--Jakob disease (CJD) can be fractionated by using a simple 1-day method that includes lysis with N-lauroylsarcosine. Unique fibrils have been identified previously in scrapie- and CJD-infected tissue. These fibrils were abundant in final fractions. Preparations from human CJD autopsy material and from experimental hamster and guinea pig CJD all displayed readily identifiable fibrils that were not seen in control preparations. Thus, these methods appear to be of value in biopsy diagnosis of suspected human cases of CJD. Lysis with N-lauroylsarcosine quantitatively solubilized infectivity from membrane-rich fractions. Significant infectivity was recovered in microfractionations. After proteinase K digestion, a diffuse band at 29 kDa was detectable on NaDodSO4/PAGE. This 29-kDa material was not present in uninfected control brain and was similar to that seen in scrapie. Protein blots of human, guinea pig, and hamster CJD fractions were tested with an antibody raised against a 29-kDa band from mouse scrapie; 29-kDa proteins were labeled in all CJD and scrapie fractions but not in controls. These results indicate that specific proteins in both these diseases share common antigenic determinants. Ricin and wheat germ agglutinin, but not concanavalin A, also labeled a portion of the 29-kDa band from hamster CJD and hamster scrapie fractions, but they did not label any bands in normal hamster fractions at the same gel protein loads. When proteinase K treatment was omitted, specific bands of ≈ 35 kDa were detected in CJD samples. These results are consistent with the idea that some CJD- and scrapie-specific proteins are glycoproteins or sialoglycoproteins that can reside in or possibly derive from cell membranes.