INFECTIONS
January 7, 2011

XMRV and CFS: RIP?

The supposed link between chronic fatigue syndrome and the XMRV virus may be simply the result of lab contamination.

Yet another study has cast doubt on previous research suggesting that chronic fatigue syndrome is caused by a mouse virus called XMRV. The new study suggests why the link to the XMRV virus appeared: it attributes the earlier results to laboratory contamination of patient samples.

The new study does not prove that the samples in earlier studies were contaminated. What it does show is how easily human samples can be contaminated with mouse DNA in general and XMRV DNA in particular in a laboratory environment. It also calls into question whether the XMRV virus is even capable of causing an infection in humans.

In order to obtain a sufficient amount of DNA to work with, the DNA in the original sample is is copied many times over by adding a mix of enzymes. This process has the potential both to introduce contaminants and to exaggerate any existing contamination.

It's been shown that XMRV can infect different types of cells grown in the laboratory, but it's never been shown that XMRV can cause infections in people.

A link between XMRV and chronic fatigue was suggested when a 2009 study found the virus present in the blood of two-thirds of all chronic fatigue sufferers in the study. XMRV has also been detected in samples from humans with prostate cancer. But the suggested link has always been controversial because of the failure of other studies to detect the virus in chronic fatigue or prostate cancer patients and because of inconsistent detection of the virus in healthy control samples.

A January, 2010 study found no XMRV in 186 patients with chronic fatigue syndrome and two other studies published in February also failed to find the virus in chronic fatigue patients.

The new British study once again challenges the alleged viral link.

The researchers point out that the XMRV DNA that has been found in patient samples taken from different parts of the world is much less diverse than the XMRV DNA isolated from infected laboratory cells. Infectious viruses isolated from different people tend to have differences in their DNA structure because viruses have a high mutation rate. That's why a new flu vaccine is needed every year. The similarity between the XMRV DNA found in all patient samples suggests that it isn't an infectious agent and is more likely a contaminant.

Another complication in DNA comparisons is that in order to obtain a sufficient amount of DNA to work with, the DNA in the original sample is amplified–it is copied many times over by adding a mix of enzymes. This process has the potential both to introduce contaminants and to exaggerate any existing contamination.

The researchers suggest that future experiments on XMRV and chronic fatigue syndrome could overcome contamination questions by running more rigorous controls and containment procedures, as is commonly done when DNA is recovered or analyzed from samples of ancient material.

In their paper, the researchers frame their conclusions somewhat tentatively: "We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result of PCR contamination with mouse DNA .... We propose that XMRV might not be a genuine human pathogen." In an interview with Reuters, one researcher gave a much stronger interpretation: "Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome. All our evidence shows that the sequences from the virus genome in cell culture have contaminated human chronic fatigue syndrome and prostate cancer samples."

A provisional PDF of an article detailing the study was published online by the open-access journal Retrovirology on December 20, 2010 and is freely available. The journal also published five other pieces dealing with XMRV, disease and contamination in December. And the 1st International Workshop on XMRV was held in September.

The end of the story of XMRV has not yet been written. More importantly – and unfortunately – the end of the story of CFS is nowhere in sight.

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