August 30, 2010

Viruses Found in Chronic Fatigue Syndrome Patients

Photo of an exhausted man

New research supports the idea that viruses may play a role in chronic fatigue syndrome (CFS), a debilitating disease that affects millions of people nationwide.

CFS is characterized by profound fatigue that doesn't improve with bed rest and can be made worse by physical or mental activity. Other symptoms associated with CFS include cognitive deficits, impaired sleep, myalgia, arthralgia, headache, gastrointestinal symptoms and tender lymph nodes.

No definitive cause for CFS has yet been identified. Last October, a team of scientists identified a murine leukemia virus (MLV)-related virus called XMRV in blood samples from patients with CFS. However, other research groups were subsequently unable to find MLV-related virus gene sequences in CFS patients.

Dr. Shyh-Ching Lo of the U.S. Food and Drug Administration (FDA) decided to test frozen samples of blood taken from well-documented CFS patients around 20 years ago. At the time, his team had been looking for, but was unable to find, agents associated with CFS. Lo’s team collaborated on the study with Dr. Harvey J. Alter at NIH's Clinical Center (CC). Their work was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the De Young Foundation.

Using a technique called PCR, the researchers searched for DNA sequences from MLV-related viruses in both patients and healthy donors. Any positive findings were confirmed by a more careful sequencing analysis. As reported in the early online edition of Proceedings of the National Academy of Sciences on August 23, 2010, the scientists found MLV-like virus gene sequences in 32 of 37 (86.5%) of the CFS patients, compared with only 3 of 44 (6.8%) healthy donors. In contrast to the study that first linked XMRV to CFS, the researchers found a more genetically diverse group of MLV-related viruses.

The team next tested samples taken nearly 15 years later from 8 of the patients who had tested positive. They found that 7 of them tested positive again. However, the viruses had changed within the patients over that time. Such changes aren’t surprising for this kind of quickly evolving virus, the researchers say.

"We have to emphasize as we did in the paper that we have not proven causality for this agent," Alter says. However, these findings do support the earlier study's results."At the same time," he notes," other laboratories have not found this, including the CDC, so a dilemma at present is how to reconcile that some labs find this association and others do not."

It's possible that the scientists have found an association with something that doesn't actually cause CFS, or that only does so in some patients. "At this point, we just don't know," Alter says. "We haven't studied enough people." Complicating the matter is the fact that no specific test is yet available to confirm that someone has CFS.

NIH is now leading an effort to test and develop standardized laboratory techniques for detecting MLV-like viruses. Among several ongoing studies, Alter's group is now screening blood donors for evidence of transmission to recipients. If these viruses do cause CFS, protecting the blood supply will be a top priority.

—by Harrison Wein, Ph.D.

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