Prions: When Good Proteins Go Bad

by Kristin Henry

A brief overview

While a bacteria reproduces itself within the host's body, and a virus takes over the host's cellular machinery, an infectious prion causes trouble for the host in a different way. An infectious protein changes the conformation (shape) of it's natural cellular analog.

Studying Scrapie (a prion disease in sheep), Stanley Prusiner and his colleagues discovered that a single protein transmitted the disease. They named it PrP(1), and found that it existed in two forms: normalPrP and scrapiePrP(1).They have the same amino acid sequence, and differ mainly in conformation (1). While the normalPrP folds mainly into alpha helices, the scrapiePrP folds into beta strands and sheets and resists digestion by proteases(1).

Isolating and identifying proteins is one thing. Explaining how a protein, without transfer of genetic material, can be replicated in the infected host is another matter. It appears that the gene for normalPrP, is on the host's chromosome, and that normalPrP does not cause disease. In a test tube, normalPrP can be converted to scrapiePrP by mixing them together(1). When scrapiePrP contacts normalPrP it causes it to unfold and then refold into Scrapie shape. This initiates a cascade with newly converted PrP converting other normalPrP(1).

NormalPrP can be found in follicular dendritic cells (FDC's) of the spleen(2). These immune system cells may be the "principal sites for prion replication in the spleen"(3), before moving into the central nervous system.

References:

  1. The Prion Diseases
    Prions, once dismissed as an impossibility, have now gained wide recognition as extraordinary agents that cause a number of infectious, genetic and spontaneous disorders
    by Stanley B. Prusiner
    Scientific American Online (August 1996 issue)
  2. Stopping Prions from Going Mad
    Researchers scramble to learn how to disarm the infectious agents behind mad cow disease, scrapie and their human counterpart, Creutzfeldt-Jakob disease
    by Julia Karow
    Scientific American Online (August 1996 issue)
  3. Impaired Prion Replication in Spleens of Mice Lacking Functional Follicular Dendritic Cells
    by Montrasio, et al
    Science, (v 228)May 19, 2000.
  4. Protozoa as Human Parasites web page
  5. CDC division of Bacterial and Mycotic Diseases
  6. Salmonella enteriti disInfection
  7. Viral Diseases and Their Etiologic Agent