Two studies looking for a virus that has been linked to chronic fatigue syndrome have come to opposite conclusions. In a new study in PNAS, scientists found strains of the suspected virus in 32 of 37 stored blood samples from CFS patients, and they also showed up in a few recent samples. These findings don't agree with those of another study released a couple months earlier in Retrovirology, which found no viral presence at all, suggesting that researchers still have work to do to sort this out.

CFS has been a controversial diagnosis for some time, with the debate largely raging over whether it is a physical or psychological condition. Lately, many studies have been testing the involvement of xenotropic murine leukemia virus-related virus (XMRV), which is closely related to a virus found in mice and may be associated with prostate cancer.

In the most recent research, a group of scientists applied a test for the virus to a set of 15-year-old frozen blood samples from known CFS patients. They used nested polymerase chain reaction, or PCR, to look for a specific gene sequence associated with an infection of any kind of murine leukemia virus.

The results published in PNAS showed that 32 of the 37 CFS samples tested positive for the virus, while only 3 of 44 healthy samples did. The researchers also took current blood samples from eight of the original 37 CFS patients, and seven of them tested positive again.

While these results seem encouraging for those looking to nail down a physical root cause for CFS, they follow on the heels of another experiment published in the journal Retrovirology that could not locate the virus or any related antibodies in a different set of CFS blood samples.

Part of the issue is that PCR can give different results depending on the conditions used. Different approaches to performing PCR can be highly sensitive or highly specific, and it appears that the choice of reaction conditions may make viruses appear or disappear in different samples.

The authors of the PNAS paper noted that their PCR tests were looking for a particular sequence commonly found in MLV. The sequence corresponds to the gag gene, one that the authors thought was the most distinctive part of the virus' sequence and the easiest to find.

Other studies, though, rely on finding a deletion usually found in the same area as the gag sequence. Testing for this deletion requires a more specific PCR test, and apparently the tests often turn up nothing—the PNAS paper's own samples did not have deletions that would have shown up in such a test, according to the authors.

Aside from testing methods, the nature of the virus seems to present further problems. As the divide between positive and negative CFS-viral links seems to fall somewhere in the Atlantic Ocean, many researchers think the differences between American and European procedures may be to blame, or else continental differences between manifestations of the virus.

As scientists are unable to reach a conclusion at this level, it seems that they will have to call it a draw and choose some new testing methods. For their side, the PNAS authors are advocating for a new study that would demonstrate where and how the viral genes integrate into the human genome.

They estimate that the virus copies into as few as one out of every 4,000 cells, and the exact site ranges widely, so this type of research will take quite a bit of time. It's important to emphasize that even if researchers are able to find the virus, it won't demonstrate that it causes CFS. Still, this kind of good hard look may finally put the debate to rest.

PNAS, 2010. DOI: 10.1073/pnas.1006901107

Retrovirology, 2010. DOI: 10.1186/1742-4690-7-57 (About DOIs).

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