Saturday, March 31 6:00 AM SGT

Cobras put the bite on mad cows

PARIS, March 30 (AFP) - Cobra venom has helped shed light on how scrapie, a cousin of the human form of mad-cow disease, may gain a foothold in the body, apparently by subverting a guardian in the immune system.

The new research focusses on lymph system cells suspected to be a haven for the mutant protein that causes scrapie as well as variant Creutzfeldt-Jakob disease (vCJD) -- the fatal brain disorder believed to be caused by eating beef infected with mad-cow disease.

Some scientists believe that the infective agent holes up in so-called follicular dendritic cells in the spleen, then replicates and spread through the nervous system to the brain.

Researchers at the Neuropathogenesis Unit in Edinburgh and the University of Zurich explored the molecular mechanics as to how this might work.

They used a derivative of cobra snake poison to deplete levels in laboratory mice of a key protein in the immune system.

The protein, C3, is part of the complement system, a group of some 30 proteins that have an important role in activating the body's defences against invaders.

The scientists injected the C3-depleted mice with the scrapie agent, either into the abdominal cavity via the peritoneum or directly into the brain.

Mice that had been infected through the peritoneum took far longer to develop typical scrapie symptoms of jerky, uncoordinated movements than fellow rodents who had been injected in the brain.

In addition, abdominally-injected mice had fewer of the mutant proteins in their spleens at the early stage of infection, they found.

The team suggest that the mutant works by binding on to C3 or to C1q, which is another protein in the complement system.

The complex is then "captured" by receptor surfaces on the follicular dendritic cells which recognise the C3 and C1q as friends.

In this way, the agent is able to penetrate the cell and reproduce, then enter the peripheral nerves of the nervous system and so on, up to the brain.

The finding, they said, suggests ways of blocking transmissible spongiform encephalopathies (TSEs) -- the small, enigmatic group of killer diseases to which scrapie, vCJD and mad-cow belong.

"In the early stages of infection, C3 and perhaps C1q contribute to the localisation of TSE infectivity in lymphoid tissue and may be therapeutic targets," they write

The study is published Friday in Nature Medicine, a member of the London-based Nature stable of science journals.

-- Anonymous, March 30, 2001