California BSE prion comes with a different twist

Reports of ‘mad cow’ disease in the United States erupted in the news this week after the US Department of Agriculture (USDA) confirmed that the remains of a California dairy cow had tested positive for bovine spongiform encephalopathy (BSE). This marks the fourth case of BSE identified in the US, and the first case in six years. In spongiform encephalopathy diseases, abnormally folded prion proteins accumulate in the brain, causing other proteins to deform as well. BSE has proved to be unusually adept at jumping between species; humans exposed to BSE can develop its human counterpart: Creutzfeldt-Jakob disease (CJD). In a statement released on 24 April, Karen Ross, Secretary of the California Department of Food and Agriculture said, “The detection of BSE shows that the surveillance program in place in California and around the country is working.” Food safety advocates such as Yonkers, New York, -based Consumers Union say it’s a warning sign that surveillance is inadequate and needs to be stepped up. Ross’s statement also makes a point of noting a key feature of this particular case: The infected cow carried what is known as ‘L-type’ BSE, a version of the disease that has not been detected before in the US and has so far not been associated with transmission through animal feed. As the policy debate over testing rumbles on, here is a short guide to what is known and not known about this rare strain and its unexpected appearance.

After brain tissue samples turned up inconclusive results in California, scientists at the USDA’s Veterinary Research Laboratories in Ames, Iowa ran two additional biochemical tests and got positive results for BSE. The second technique, western blotting, separates proteins based on their molecular weight to create a pattern on a gel. L-type prions have low weights, and another atypical strain, H-type prions have high weights compared to classic (C) strains. This sample produced a clear L-type pattern, said Mark Hall, head of the pathology, parasitology, and entomology section at Ames. In addition to weighing less, L-type strains also produce different lesion profiles in the brain. Both H and L types are extremely rare and found in older cattle, with only around 30 reported cases each worldwide. Perhaps this contributes to the fact that we don’t know much about them. “Right now, the full pathogenesis is not well characterized,” says Hall of L-type. Unlike their classical counterparts, “past studies and current diagnostic tests to detect ruminant DNA and RNA in feed haven’t found atypical variants,” says Jim Cullor, a veterinarian at the University of California at Davis.

“There is some evidence in primates and transgenic mice that it seems to spread faster – meaning it maybe more virulent – but we don’t know how representative these models are of the disease in humans,” says Linda Detwiler, a clinical professor at Mississippi State University’s College of Veterinary Medicine. Whether or not L-type could jump species without direct injection into the brain remains unclear, but so far it can transmit to transgenic humanized, ovinized (modified to genetically mimic sheep), bovinized, and normal mice, as well as macaques in the lab. “We do know that L-type can transmit from one cow to another through injection in the brain,” says Detwiler. “Long term studies are beginning to look at whether or not it’s capable of transmission orally through feed, but we don’t have the data yet.” Whether these strains have been around for a long time or recently developed is still unknown. “No one knows the origin at this point,” says Detwiler. “It might be sporadic, similar to sporadic types of Creutzfeldt-Jakob disease in humans. It might be some kind of genetic mutation, or it could be a modification of classical BSE or TSE.” In a 2008 study, out of all known cases of atypical BSE, only one contained a genetic mutation. So, a mutant cause can’t be ruled out and could arise in countries that have never seen BSE. In humans, sporadic cases of CJD – those that aren’t caused by transmission from cattle – occur at random in humans without a clear cause.

The USDA bans cow material in cow feed and “specific risk material” – meaning bone, brain, and other organs where the disease persists – from all livestock feed. “The L-type’s infectivity alone reinforces the need for regulations,” says Detwiler. “It’s really important to monitor any emerging disease around the world so that we can change our policies if we need to.” Some feel that the regulations aren’t enough. Michael Hansen, a senior staff scientist with Consumer’s Union, notes that only .13% of the 30 million cattle that go to slaughter annually in the US are tested. “I would argue that’s not enough,” says Hansen. “The feed ban is not a firewall.” The USDA has sent samples to official World Animal Health (OIE) reference labs in Canada and Great Britain. An on-site farm investigation may reveal more about the source and potential extent of infection. Whether or not the case produces any astounding revelations in the coming weeks, it has already underscored the many general unknowns that researchers face when it comes to L-type. “It’s important to look at whether it can transmit orally into to cattle or other species that consume feed, and to figure out where infection occurs in case we need to look for different high risk material,” says Detwiler. “With continued research and epidemiology studies, we’ll get more clues.”

May 15, 2012

Original web page at Nature