Abnormal prion proteins assumed to be the infectious agents that cause mad cow disease and variant Creutzfeldt-Jakob disease might not be to blame after all. Experiments in mice also imply that current tests to detect and intercept meat from animals infected with BSE might miss some cases if diseased animals don鈥檛 have the abnormal proteins in their brains.
鈥淭he accepted theory is that the abnormal protein is infectious,鈥� says Rona Barron, head of the team at the Roslin Institute in Edinburgh, UK, which undertook the research in collaboration with the Scripps Research Institute in La Jolla, California.
Normally when animals die of a BSE-like disease, their brains are full of holes and clogged up with abnormal prion proteins 鈥� mis-folded versions of normal brain-cell proteins. But when Barron鈥檚 team deliberately infected mice with human or hamster strains of BSE-like diseases, the mice died of the diseases but had little or no detectable trace of abnormal prion in their brains. 鈥淲hat we鈥檙e questioning now is whether the large amount [of abnormal prions] you usually see is the infectious agent itself or something produced by the disease,鈥� says Barron.
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鈥淭he mice died of BSE-like diseases but had little or no detectable trace of abnormal prion protein in their brains鈥�
The results were the same in a follow-up experiment in which Barron injected brain material from the dead mice into the brains of other mice. The mice died rapidly, proving that the injected brain material was highly infectious, but once again there was little or no trace of abnormal prion in their brains (The Journal of Biological Chemistry, ).
鈥淭his work tells us that the prion is probably the pathological consequence of infection rather than the infectious agent itself,鈥� says Laura Manuelidis of Yale Medical School, who believes virus-like particles might be responsible for diseases like BSE.
Other researchers remain convinced that a protein alone is responsible and that the prion hypothesis still holds. 鈥淲hat the research shows is that the prion we detect is not necessarily the one that has most infectivity,鈥� says Chris Higgins, chairman of the UK government鈥檚 Spongiform Encephalopathy Advisory Committee. 鈥淲e simply don鈥檛 know what the infective folded state is yet.鈥� Barron鈥檚 team hunted for other forms of mis-folded prion proteins in the mice鈥檚 brains without success.
Despite the outcome of the experiments, both Higgins and Barron say that abnormal prions are still a very good marker of disease and current tests should not be withdrawn. While they may miss some cases of BSE, they probably pick up the majority. Higgins says that thanks to the tests and the UK鈥檚 culling strategy, BSE has now been virtually eliminated from the UK.
BSE and vCJD 鈥� Learn more in our comprehensive special report.
