The link between the XMRV retrovirus and patients with chronic fatigue syndrome is probably the result of laboratory contamination, according to two new studies published today by the journal Science.
In 2009, a report that patients with chronic fatigue syndrome were infected with XMRV attracted considerable interest, but subsequent studies published in other journals by independent scientists failed to detect XMRV in other groups of patients with the condition. (Vincent Lombardi et al, Science Express 8 October 2009; Science 23 October 2009)
In one of the new studies, Tobias Paprotka of the National Cancer Institute and colleagues provide evidence that XMRV arose in the 1990s by recombination of two mouse leukemia viruses during laboratory “passage” of a human prostate tumor in mice. In order to generate more tumor tissue to study, researchers had injected the human tumor tissue into mice, grew tumors, injected that tissue into new mice, and so on, until they had large enough samples to analyze.
Paprotka and colleagues conclude that a cell line derived from one of those samples, known as 22Rv1, is the most likely explanation for the detection of the virus in patient samples. These cells contained a virus that was generated by the recombination of two mouse “proviruses” during the passaging process. And because its sequence is so similar to the XMRV sequence associated with the patients’ samples, it’s extremely improbable that the XMRV sequence came from any other source.
“Our results suggest that the association with XMRV with human disease is due to contamination of human samples with virus originating from this recombination event,” the authors write.
In independent work, Konstance Knox of Wisconsin Viral Research Group and Open Medicine Institute and colleagues examined blood samples from 61 patients with chronic fatigue syndrome. These patient samples were from the same medical practice that had supplied samples to the Lombardi research group and included 43 who had been diagnosed previously as XMRV-positive. Sensitive assays for viral genetic material, infectious virus, and virus-specific antibodies revealed no evidence of XMRV in any of the samples.
These papers are accompanied by an editorial expression of concern from Science, which notes that the Lombardi paper had a far-reaching impact on the community of patients with chronic fatigue syndrome and beyond, but that its validity is now in question. The editorial expression of concern, which is being attached to the Lombardi paper, also explains that the U.S. National Institutes of Health is sponsoring additional, carefully designed studies to ascertain whether the association between XMRV and chronic fatigue syndrome can be confirmed. Science eagerly awaits the outcome of these further studies and will take appropriate action when their results are known.
Read the new material on XMRV and chronic fatigue syndrome being published today.
Read an abstract of the Lombardi paper that’s now in question.