In 2006, the gammaretrovirus xenotropic murine leukemia virus–related virus (XMRV) was detected in human prostate tumor tissues (PLoS Pathog. 2, e25, 2006). Judy Mikovits and her colleagues from the Whittemore-Peterson Institute (WPI) then reported that this virus was also associated with chronic fatigue syndrome (CFS) (Science 326, 585–589, 2009). They found XMRV DNA in two thirds of the blood samples from individuals with CFS that they examined, as well as evidence of XMRV infectivity and patient immune responses to a closely related virus, spleen focus-forming virus. The WPI findings were debated as a flurry of subsequent reports failed to reproduce the results. In response, the US National Institutes of Health (NIH) has initiated a multicenter, blinded, large-scale study to compare blood samples from individuals with CFS to those from healthy subjects, with the results expected later this year.

Now, two new papers indicate that XMRV was a contaminant in the initial WPI study. The first of the studies could not find any evidence of XMRV infection in the same samples tested by the WPI (Science doi: 10.1126/science.1204963, 2011). The authors also found that XMRV and related gammaretroviruses are inactivated by sera from people with CFS, indicating that these viruses are unlikely to establish an infection in humans. An independent study showed that XMRV probably arose as the consequence of a recombination event between two mouse proviruses during the passaging of human prostate tumor xenografts through mice (Science doi: 10.1126/science.1205292, 2011). This recombination event occurred between 1993 and 1996, long after the first diagnosis of CFS.

When the WPI article was published, many scientists advised that further investigation would be necessary before moving forward to translate the findings. Others were not so cautious: a WPI-owned company now offers a test (costing up to $549) to detect XMRV DNA in people with CFS, although it is unclear what benefit such knowledge would provide. Despite undesirable side effects and a lack of evidence of clinical benefit, some doctors have prescribed antiretroviral drugs to patients with CFS on the basis of the observation that antiretrovirals can inhibit XMRV replication in vitro (PLoS ONE, 5, e9948, 2010). Some blood banks have prohibited people with CFS from donating blood in response to an advisory from the AABB (formerly the American Association of Blood Banks), an international association of blood banks, and an advisory committee recently recommended that the US Food and Drug Administration should follow suit. All of these measures now seem premature, given the questionable strength of the data supporting them.

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