Properties of the Prions - Slow Diseases Caused by Prions

Properties of the Prions

Prions are small protein-containing infectious particles with no detectable nucleic acid. They were suspected to be viruses but otherwise do not conform to the standard definition of viruses. They differ from the viruses in their many properties (Table 69-2). The prions show following characteristics:

a)        Prions like viruses are filterable.

b)       They apparently lack any virion structure or genome.

c)        Unlike viruses, they are unusually resistant to inactivation by heat, disinfectants, and radiation.

d)       They do not elicit any specific immune response in the infected host.

◗ Morphology

Different hypotheses have been suggested for the makeup of prions. Initially many research workers considered prions to be (a) nucleic acid only, (b) protein only, (c) lacking both protein and nucleic acid, and (d) polysaccharide. Currently, the most widely accepted hypothesis is the “protein only hypothesis” first suggested by Griffith (1965) and re-established subsequently by Prusiner to indicate that scrapie is related to a proteinaceous infectious particle (PrP). Prions show following features:

·           The prion does not contain any nucleic acid.

·           It contains an aggregate of hydrophobic glycoprotein, resistant to protease.

·           The protein present in humans and other animals is called cellular prion protein. It is similar to glycoprotein in scrapie known as scrapie prion protein, which has a molecular weight ranging from 27,000 to 30,000 Da. It is similar to scrapie prion protein in its protein sequence but differs from it in being sensitive to protease (scrapie protein is protease resistant) and being present in plasma membrane (scrapie prion protein is present in cytoplasmic vesicles).

◗ Prion replication

In experimental animal studies carried out in chimpanzees, Prusiner demonstrated conclusively that the prion, an aberrant protein, could cause disease, for which he was awarded Nobel Prize in 1997. 

Prusiner hypothesis suggests that prions do not contain any nucleic acid. The normal prion protein known as prion protein cellular or PrPChas a significant amount of helicalconfiguration. In its alpha-helical configuration, PrPC is usually sensitive to degradation by the activity of enzyme protease. Disease occurs when the PrPC is reconfigured into the beta-sheet configuration known as prion protein scrapie or PrPSC, which is resistant to degradation by protease.

These abnormal proteins are resistant not only to protease degradation but also to radiation, heat, and other agents that destroy proteins. These aggregate into filaments that disrupt neuron functions and cause death of cells. Both the normal alpha-helical form and the abnormal beta-pleated sheet form have the same amino acid sequence but differ in their configuration.

◗ Other properties

Prions, unlike viruses, are unusually resistant to heat at 80°C, ultraviolet radiation, and disinfectants, such as formaldehyde. They are, however, inactivated by phenol, ether, sodium hydroxide, and hypochlorite.

Prion Isolation

Prions cannot be cultivated in any tissue culture or isolated in any experimental animal models.