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Studies Refute Virus' Link to Chronic Fatigue Syndrome

TUESDAY May 31, 2011 -- A virus identified two years ago as a possible cause of chronic fatigue syndrome now turns out not to be the culprit, new research says.

Experts say it's a major setback in the effort to understand and treat this mysterious and debilitating disease.

The authors of a new study published May 31 in Science find that the so-called XMRV viral pathogen spotted in human samples in the prior study (published by the same journal in 2009) likely got there as a result of "genetic recombination." That can occur in the laboratory when DNA from different viruses mix.

In this case, two mouse viruses combined and the product of that union then contaminated the human specimens via "reagent" compounds used in the lab, the new research shows.

This probable contamination of the samples with XMRV in the lab "means that this virus has no proven association" with chronic fatigue syndrome, said Stuart LeGrice, head of the lab that oversees all XMRV research at the U.S. National Cancer Institute, which conducted the new study.

"I believe the evidence is incontrovertible," he added. "It doesn't rule out the possibility that there's another retrovirus [involved] but, as of right now, we're close to 100 percent certain that this eliminates the virus as a causative agent of either condition."

The study was accompanied by a rare "Expression of Concern" from the editors of Science. While they did not call for an outright retraction of the original paper, the editors pointedly questioned the study's validity.

According to the Wall Street Journal, the editors of Science have asked the authors of the 2009 paper to voluntarily retract their paper. The authors have responded that any retraction would be "premature," the newspaper reported.

This sequence of events began two years ago, with the publication of a finding that about two-thirds of patients with chronic fatigue syndrome sampled were infected with XMRV, which stands for xenotropic murine leukemia virus-related virus. These viruses can cause cancer and other problems in mice and they can infect human cells in the laboratory.

At the time, the finding raised hopes that there might finally be a concrete cause for chronic fatigue syndrome and perhaps, down the line, treatments for the disease.

The illness affects an estimated 1 percent of people worldwide and, as its name implies, involves crippling fatigue as well as aching joints, headaches and various other symptoms.

Unfortunately, subsequent studies by other researchers failed to replicate the findings.

The authors of the new study looked at blood samples from 61 people with chronic fatigue syndrome. The samples came from the same source that had supplied samples for the 2009 study. Forty-three of the samples had earlier been diagnosed as positive for XMRV.

However, this time around the researchers avoided using any lab products derived from mice. This time, they found no evidence at all of XMRV in any of the 61 samples.

"We're learning a very important lesson that even some commonly used reagents [compounds used in scientific experiments] contain trace amounts of contaminating mouse DNA," said LeGrice, who is head of the Center of Excellence in HIV AIDS/Cancer Virology at the National Cancer Institute. "But, using diagnostic technologies that are ultra-sensitive, we can easily pick out the contaminating material. The contaminants somehow got into the samples [but] we have to be absolutely clear that this virus was never in humans."

A second study in the same issue of the journal had similar problems trying to replicate earlier research linking XMRV with prostate cancer tumors, for much the same reasons. That study was led by Jay Levy of the University of California, San Francisco.

A statement from the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America said that "these studies add to the mounting number of publications that challenge the reliability of the initial report."

The U.S. National Institutes of Health is sponsoring additional studies on XMRV and chronic fatigue syndrome.

"We will support the outcome of those studies, whichever way they lead," the CFIDS statement said.

More information

There's more on chronic fatigue syndrome at the U.S. Centers for Disease Control and Prevention.

Posted: May 2011


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