XMRV doesn't cause chronic fatigue

Two studies point to contamination of patient samples as the cause of a controversial 2009 finding that linked the mouse virus XMRV with chronic fatigue syndrome

By | June 3, 2011

Two studies have cast further doubt on a 2009 report that a mouse virus is linked to chronic fatigue syndrome. The studies, both published Tuesday (May 31) in Science, point to lab contamination as the source of xenotropic murine leukemia virus-related virus, or XMRV, in cell samples from chronic fatigue patients.
Microscopic image of XMRV (Xenotropic murine leukemia virus-related virus)
Image: Wikimedia commons, Center for Disease Control and Prevention
As a result of these findings, both the scientific community and chronic fatigue patients "will ultimately have to accept the scientific proof that there's just no hint of a connection to that disease," linkurl:Stephen Goff,;http://www.microbiology.columbia.edu/faculty/goff.html a virologist at the Columbia University Medical Center in New York who was not involved in the study, told The Scientist. In 2009, a team led by Judy Mikovits of the Whittemore Peterson Institute linkurl:reported that;http://www.sciencemag.org/content/326/5952/585.abstract 67 percent of CFS patients, but only 10 percent of healthy controls, tested positive for XMRV. The results caused a flurry of excitement in the chronic fatigue community, and some patients even started on HIV antiretroviral drugs in an effort to fight the disease. But follow-up studies failed to replicate the findings. The new studies prompted Science to issue an linkurl:Editorial Expression of Concern,;http://www.sciencemag.org/content/early/2011/05/31/science.1208542.full.pdf and the journal's editor-in-chief Bruce Alberts has asked the authors of the original paper for a retraction, linkurl:according to the Wall Street Journal .;http://online.wsj.com/article/SB10001424052702303745304576355852212887170.html In response, Mikovits sent a letter saying that retracting the paper would be premature, arguing that five separate labs conducted the original study that found an association between CFS and XMRV, and that all reagents and cell lines were screened for both mouse and gammaretrovirus contamination. In linkurl:one of this week's studies,;http://www.sciencemag.org/content/early/2011/05/31/science.1204963 researchers led by linkurl:Jay Levy,;http://ari.ucsf.edu/science/scientists_levy.aspx a professor of medicine atthe University of California, San Francisco, analyzed samples from 61 chronic fatigue patients from the Whittemore Peterson Institute, including 43 people that previously tested positive for the retrovirus. They found no hint of XMRV infection in any of them, despite using several detection methods. They also tested a random sample of reagents that are used in many labs to detect the virus (though not the exact ones used in the original study) and found many had mouse DNA , Levy said, suggesting that such products are prone to contamination. Because early reports of XMRV appeared in prostate cancer cells, linkurl:the second paper;http://www.sciencemag.org/content/early/2011/05/31/science.1205292 tested frozen tumor cell lines to traced the virus's origins and concluded it formed in a lab by the recombination of two mouse viruses in the 1990s. CFS, on the other hand, has been known since at least the mid 1980s, said team leader linkurl:Vinay K. Pathak,;http://home.ncifcrf.gov/hivdrp/Pathak.html, a virologist at the National Cancer Institute in Frederick, Maryland. In fact, some of patients tested in the 2009 study were diagnosed with CFS before the virus was formed. The new findings don't rule out an infectious agent as the cause of chronic fatigue syndrome, Pathak said. "We're just saying it's not this virus." K. Knox, et al., "No evidence of murine-Like gammaretroviruses in CFS patients previously identified as XMRV-infected," Science,DOI: 10.1126/science.1204963, 2011. T. Paprotka, et al.,"Recombinant origin of the retrovirus XMRV," Science, DOI: 10.1126/science.1205292, 2011.
**__Related stories:__***linkurl:Viral cause for chronic fatigue?;http://www.the-scientist.com/blog/display/56048/
[8th October 2009]*linkurl:Q&A: Why I delayed XMRV Paper;http://www.the-scientist.com/blog/display/57628/
[23rd August 2010]*linkurl:CDC Downplays XMRV, chronic fatigue link;http://blog.the-scientist.com/2010/07/06/news-in-a-nutshell-5/
[6th July 2010]*linkurl:Viral cause for prostate cancer?;http://www.the-scientist.com/news/display/55966/
[7th September 2009]


Avatar of: Wallace Sampson

Wallace Sampson

Posts: 1

June 4, 2011

One heluvalot of trouble could have been avoided looking for XMRV - or not - in chronic fatigue (CFS) by a reading of U. Toronto historian Edward Shorter's book, From Paralysis to Fatigue as well as others - American Nervousness - and numerous journal papers. \n\nShorter traced the history of somatiform disorders from the 19th century and Freud to the 1980s false CFS epidemic. CFS did not start in 1985, but was given the name and criteria by personnel at the Center for Disease Control in order to trace the recent epidemiology of the disorder. \n\nSomatiform illness (CFS) has been documented in its varying forms as a somatic reaction (symptom generation) of unknown cause, but is known to have a large psychogenic overlay in most affected people. Its name has also varied with the symptoms, which have been comensurate with symptoms acceptable to physicians at the time as physical. Its varying appearances have been named from encephalomyagia, to Icelandic disease, and attributed to a variety of viruses (cytomegalovirus, Epstein-Barr, several HRVs, and bacteria (brucella) and fungi (candida,) and metabolic disorders (hypothyroidism, hypoglycemia,) and external toxins (multiple chemical sensitivities.) \n\n Separate from the confusion as to the reality and etiology of somatiform illness as described was the credibility of the 2009 Science study. Some of us predicted the study would not be replicated (Sampson W. CFS: viral vs. somatization. Sciencebasedmedicine.org, Oct.14, 2009, accessed 6/4/2011.) The reasons were several, including some authors having reported prematurely and erroneously other viral causes, as well as the original non-epidemic; and the fact that the scientists identifying the XMRV in CFS subjects were inexperienced at clinical research and the necessary precautions and possible sources of error. Serendipitously (?) a paper came within a few days later showing the high potential for laboratory contamination by the XMRV.\nThe point again: Since there are no criteria for disproof of anomalous findings other than expensive, repeated non-replications, knowledge of the underlying basic sciences and histories of dubious claims should be incorporated into the probability of a finding being valid. \n
Avatar of: Peter Pedersen

Peter Pedersen

Posts: 2

June 13, 2011

The gammaretrovirus direction was always contentious with the neuroendocrinologists (that I work with).\nWallace, thank you for a concise précis of the overarching confusion/classification of CFS, my clinical specialty since 1985 under guidance of Prof William Vayda \nI have researched endogenous endocrinopathy and treat with organic glandular extracts. Modest success rate...60% resolution over avg 2 years. enjoying this development as it removes an unnecessary discussion.

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