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Immunoaffinity purification and neutralization of scrapie prion infectivity.

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  • 1. Department of Neurology, University of California, San Francisco 94143.
      Authors
    • Gabizon R 1
    (1 author)

Proceedings of the National Academy of Sciences of the United States of America, 01 Sep 1988, 85(18):6617-6621
https://doi.org/10.1073/pnas.85.18.6617 PMID: 3137571 PMCID: PMC282028

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This article has been corrected. See Proc Natl Acad Sci U S A 1989 Feb;86(4):1223.

Abstract 

Prions are unusual infectious pathogens causing scrapie of sheep and goats as well as Creutzfeldt-Jakob disease of humans. Biochemical and genetic studies contend that the scrapie isoform of the prion protein (PrPSc) is a major component of the prion. Limited proteinase K digestion of PrPSc produced a protein of 27-30 kDa. After dispersion of brain microsomes isolated from scrapie-infected hamsters into detergent-lipid-protein complexes, copurification of PrPSc and scrapie infectivity was obtained with scrapie prion protein of 27-30 kDa monoclonal antibody-affinity columns. PrPSc was enriched approximately equal to 5700-fold with respect to total brain protein, whereas scrapie prion infectivity was enriched approximately equal to 4000-fold. The ratio of prion titer to PrPSc remained constant throughout purification. Heterologous monoclonal antibody columns failed to bind either PrPSc or scrapie infectivity. Polyclonal rabbit prion protein antiserum raised against NaDodSO4/PAGE-purified scrapie prion protein of 27-30 kDa reduced scrapie infectivity dispersed into detergent-lipid-protein complexes by a factor of 100. These results represent direct immunologic and chromatographic demonstrations of a relationship between PrPSc and prion infectivity as well as providing additional support for the contention that PrPSc is a major component of the infectious scrapie particle. That PrPSc is a host-encoded protein is an important feature distinguishing prions from viruses.

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Proc Natl Acad Sci U S A. 1988 Sep; 85(18): 6617–6621.
PMCID: PMC282028
PMID: 3137571

Immunoaffinity purification and neutralization of scrapie prion infectivity.

R Gabizon, M P McKinley, D Groth, and S B Prusiner
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Abstract

Prions are unusual infectious pathogens causing scrapie of sheep and goats as well as Creutzfeldt-Jakob disease of humans. Biochemical and genetic studies contend that the scrapie isoform of the prion protein (PrPSc) is a major component of the prion. Limited proteinase K digestion of PrPSc produced a protein of 27-30 kDa. After dispersion of brain microsomes isolated from scrapie-infected hamsters into detergent-lipid-protein complexes, copurification of PrPSc and scrapie infectivity was obtained with scrapie prion protein of 27-30 kDa monoclonal antibody-affinity columns. PrPSc was enriched approximately equal to 5700-fold with respect to total brain protein, whereas scrapie prion infectivity was enriched approximately equal to 4000-fold. The ratio of prion titer to PrPSc remained constant throughout purification. Heterologous monoclonal antibody columns failed to bind either PrPSc or scrapie infectivity. Polyclonal rabbit prion protein antiserum raised against NaDodSO4/PAGE-purified scrapie prion protein of 27-30 kDa reduced scrapie infectivity dispersed into detergent-lipid-protein complexes by a factor of 100. These results represent direct immunologic and chromatographic demonstrations of a relationship between PrPSc and prion infectivity as well as providing additional support for the contention that PrPSc is a major component of the infectious scrapie particle. That PrPSc is a host-encoded protein is an important feature distinguishing prions from viruses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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