29 March 1996

Altered protein is cause of disease

What causes spongiform disease?

Not a virus or bacterium. Its caused by abnormal production of a normal protein made in the brain, spinal cord, and intestines.

The altered form of this protein is called a prion. This infectious protein particle is thought by some scientists to convert normal protein molecules in the brain into its own malignant form. Aggregates of this altered protein are visible as deposits under the electron microscope. Whether this prion protein is the cause of the disease or one of its effects is still unknown. It could be that there is an infectious agent carried on the prion that is causing the disease.

US work has shown that mice without this special protein dont succumb to the disease despite being challenged with the infectious prion agent.

Species barrier

This is a natural obstacle to transmission between species. The barrier has two components. The first is the difference in the amino acid sequence of the gene that codes for the host protein (PrP) in donor and recipient species. In sheep this gene exists in several versions.

Sheep carrying one version have proved to be susceptible to developing the prion disease scrapie, while those with another version are resistant. There is no evidence, however, that the gene varies in cattle making each equally susceptible to BSE. The sequence of the gene varies between species. As a result, so does PrP. We know that PrP gene sequence in sheep and cattle are similar and both are different from the human PrP gene.

The second contribution to the barrier is the strain of the agent. The BSE agent which has only one strain, is different from the 20 or so strains of the scrapie agent.

Scientists now hope to compare human and bovine strains of spongiform disease by studying their effects on mice at the Institute of Animal Health.

If a sample of BSE and one of a CJD produce similar disease progression, this will be considered as good evidence that they are the same strain and confirm a cross infection that has broken the species barrier.

Its success in jumping that barrier depends on three factors (see box).