A virus that originates in mice, which last year was hailed as a possible cause of chronic fatigue syndrome, or ME, is not the cause of the disease, say scientists.
Four papers published by the journal Retrovirology all come to the conclusion that the finding of the mouse virus XMRV in human cell samples was not the breakthrough that researchers and doctors had hoped for. Further research suggests that the samples were contaminated with mouse DNA.
"Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome," says Professor Greg Towers, a Wellcome Trust Senior Research Fellow at University College London (UCL) and an author of one of the papers.
"All our evidence shows that the sequences from the virus genome in cell culture have contaminated human chronic fatigue syndrome and prostate cancer samples.
"It is vital to understand that we are not saying chronic fatigue syndrome does not have a virus cause – we cannot answer that yet – but we know it is not this virus causing it."
The discovery of xenotropic murine leukemia-related virus (XMRV) in patients with CFS by the Whittemore Peterson Institute in Reno, Nevada, published in the highly reputable journal Science, set the CFS/ME community alight. Many people who had been desperately ill for years without any idea of the cause, believed that this could be the answer. With a viral cause, CFS should be treatable and preventable.
But attempts to replicate the institute's findings have largely failed and the four papers published today leave little scope for further work on XMRV.
"Studies conducted by four completely independent research groups working around the globe have all reached the same conclusion: it is likely that the evidence for mouse virus found in human samples was due to contamination by mouse DNA," says Mark Wainberg, editor of the open-access journal Retrovirology.
The research includes evidence from a team led by Professor Myra McClure from Imperial College, London who looked at samples from prostate cancer patients, where XMRV had also been identified. They noted that XMRV was routinely found in around 5% of US citizens with prostate cancer, but was only very rarely found in European patients. Analysing British, Korean and Thai samples with a highly sensitive assay technique, however, revealed markers for mouse DNA other than XMRV. Professor Brigitte Huber and her team from Tufts University, near Boston, found similar results in samples from CFS patients.
In another paper, Dr Takayuki Miyazawa from Kyoto University offered evidence that the mouse DNA contamination may come from a particular manufacturer of testing kits commonly used to identify XMRV in tissue samples. When analysing the reagents in the kits without any human tissue present, the team found markers for mouse DNA.
The fourth paper came from Greg Towers and colleagues at UCL. They carried out retrospective analysis of previous research that seemed to support the claim and found that mouse DNA contamination was very likely in most of these studies. They concluded that researchers have been trying to identify XMRV using a DNA marker that may not be unique to XMRV after all. "Collectively, these results cast serious doubts on the PCR evidence used to support claims of MLV- related viruses in prostate cancer and CFS patients," writes Prof Robert Smith, Department of Pathology, University of Washington, Seattle in the USA in an editorial. "Future assessments of the prevalence of XMRV should include more rigorous PCR and phylogenetic tests to exclude the possibility of contamination."
