More MS news articles for May 2001

Double whammy could cause MS

http://www.nature.com/nsu/010524/010524-13.html

Wednesday 23 May 2001
TOM CLARKE
American Society for Microbiology General Meeting, Florida

A well-timed one-two punch from viruses may cause multiple sclerosis (MS), researchers suggested at this week's American Society for Microbiology annual meeting in Orlando, Florida.

MS occurs when the body's immune system turns against the protein myelin, which insulates our nerve cells. Viral infection of some form has long been suspected as the trigger for this auto-immune response, but no single virus has yet been linked to the disease.

That, says Robert Fujinami of the University of Utah in Salt Lake City, may be because two separate viral infections are required to confuse the immune system into destroying healthy nerve cells. "One virus silently primes for auto-immune disease that is then triggered by later viral infections," says Fujinami.

The epidemiology and inheritance of MS have long pointed to an infectious origin for the disease. Studies with identical twins show that if one twin develops the disease the other has only a 30% chance of getting it, suggesting that genes are only partly responsible.

And, although the disease is more prevalent among Europeans, the risk is reduced in those who move towards the equator early in life. What's more, viral infections such as influenza are known to cause MS symptoms to flare.

The Utah team hypothesize that the immune system is primed for causing MS by an infection early in life with a virus that has proteins strongly resembling myelin.

Although this infection alone doesn't cause disease, they propose, it programs the CD4+ immune cells to recognize myelin as non-self.

If another virus later stimulates the immune system to replicate the primed CD4+ killer cells they will the set about attacking myelin, leading to MS.

To test the theory, Fujinami's team infected mice susceptible to MS with a virus that was engineered to contain myelin-like surface proteins. As expected, the virus did not damage nerve cells.

When the same mice were given a benign cowpox virus one with no molecular similarity to myelin proteins the researchers saw a rapid inflammation in the animals' brain tissue, the mouse equivalent of MS.

Fujinami's team thinks that the secondary viral infection causes the production of a molecule, interleukin-12, that stimulates dormant CD4+ cells. A wealth of viruses, even those that cause respiratory infections, can stimulate interleukin-12 production.

The triggering of MS by a double-whammy of infection would explain why "no one virus has been ascribed as a cause for MS," says Fujinami. And, as MS affects people between the ages of 20 and 40, there must be a narrow window for the secondary infection early in life, he reasons.

While there are limitations to mouse models of MS, Fujinami's work is "definitely heading the the right direction," according to Peter Riskind, associate director of the multiple sclerosis clinic at the University of Massachusetts Memorial Health Center in Cambridge, Massachusetts.

If the model proves correct it may be possible to identify the types of virus that cause exacerbations and to develop antiviral therapies against them to lower the number of attacks in MS sufferers. Similarly, if researchers could identify the types of virus that prime the immune system they might even be able to vaccinate against them, preventing MS altogether.