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From: TSS ()
Subject: Cause of prion diseases could be viral
Date: January 30, 2007 at 8:13 am PST

Cause of prion diseases could be viral

Study questions common chronic wasting theory

By JOHN FAUBER
jfauber@journalsentinel.com
Posted: Jan. 29, 2007

Researchers have found virus-like particles in the brain tissue of animals infected with so-called prion diseases, including the fatal human disorder Creutzfeldt-Jakob disease, a finding that calls into question a controversial theory that the diseases are caused by rogue proteins devoid of genetic material.


Although the finding does not disprove the prion theory, it provides evidence of a "very strong alternative," said lead author Laura Manuelidis, a professor of neurobiology at Yale University Medical School.
Manuelidis, whose work appears today in the Proceedings of the National Academy of Sciences, said the same slow-acting viruses most likely also cause chronic wasting disease, the fatal brain disease that has infected the wild deer herd in Wisconsin and other states.

"Everybody has been ignoring these (virus-like particles) for years," Manuelidis said. "The final proof is not in, but there is a lot of evidence (of a viral cause)."

If the virus theory were to hold up, it could lead to new ways to test for mad cow disease and chronic wasting disease.

The new research used electron microscopy to examine cell cultures from mice that were infected with scrapie, a brain disease in sheep, and Creutzfeldt-Jakob disease, a similar disorder in people. They found an abundance of small virus-like particles.

These virus-like particles were able to induce brain disease when injected into hamsters, Manuelidis said. The particles also did not bind to the antibodies of normal prion protein. That suggests they contained no prion protein and that only the virus could be the infectious agent, Manuelidis said.

The virus-like particles found in the cell cultures were small, roughly the size of the polio virus, said Sheldon Penman, a virologist and emeritus professor of biology at Massachusetts Institute of Technology.

Building a case
Penman, who submitted the Manuelidis paper to the National Academy, said he has been following her work for years as she slowly has built a case that prion diseases, known formally as transmissible spongiform encephalopathies or TSEs, are caused by a virus rather than a protein-only substance.

Penman noted that virus-like particles first were observed in TSE-infected brain tissue decades ago, but they were largely ignored as the field became focused on the prion theory.

"It shows we should go back and consider that this is a viral disease," Penman said. "The idea that it's an infectious protein is ridiculous."

The new research is suggestive but not compelling, said Judd Aiken, a prion researcher at the University of Wisconsin-Madison.

It still needs to be shown that the particles have nucleic acid, Aiken said.

"The article shows there's clearly some debate," he said. "But I'm skeptical."

He said most scientists in the field accept the prion theory, although some agree that it, too, has yet to be fully proven.

If it turns out the TSEs are caused by a virus, it would have enormous implications, Aiken said. For instance, testing for disorders such as mad cow and chronic wasting disease would be much simpler and reliable, he said.

Stanley Prusiner first proposed that a rogue protein molecule devoid of nucleic acid could replicate itself and cause the family of fatal brain disorders in people and animals. This abnormally shaped protein caused disease, he said, simply by inducing another protein in the brain to mimic its deformed shape.

His revolutionary idea won the Nobel Prize in 1997, although a few researchers have remained unconvinced.

Proof is tough to find
Three years ago Frank Bastian, a professor of neuropathology at Tulane University, found bacteria known as spiroplasma in brain tissue samples from people and animals that died of TSEs, including chronic wasting disease, scrapie in sheep and Creutzfeldt-Jakob disease in people. However, no one else has duplicated his research.

So far Bastian has shown only an association between spiroplasma and TSE diseases. He has not proved that the organism causes the disease.

But evidence of the infectivity of prions also has been indirect. No one yet has been able to fully purify and isolate prions from infected brain tissue and show that they cause disease.

A spokeswoman for Prusiner, a researcher at the University of California, San Francisco School of Medicine, said he was not available to comment on the new paper because he does not do media telephone interviews.

Neurobiologist Kamel Khalili said he has seen the electron microscopy images from the new paper and the particles certainly look like viruses.

There is a large body of evidence supporting the prion theory, albeit circumstantial, he said. "We must always keep our minds open," said Khalili, chief of neuroscience at Temple University School of Medicine.

http://www.jsonline.com/story/index.aspx?id=558662


TSS



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