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XMRV Papers Retracted

01/11/2012
Ansa Varughese

Two papers that reported a link between a retrovirus and chronic fatigue syndrome have been retracted, reducing the data that supports such a link.

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Two papers that proposed a link between chronic fatigue syndrome (CFS) and a virus related to xenotropic murine leukemia virus (XMRV) have been retracted.

Last month, Science fully retracted a 2009 paper that reported the detection of the retrovirus called XMRV in the blood cells of patients with CFS (1–2). Soon after its publication, the paper drew strong criticism from the scientific research community, including dozens of laboratories from around the world who failed to replicate the study’s findings and claimed the findings were the result of contamination.

In this section from a human prostate cancer, XMRV proteins are expressed in infected cancer cells. Cells showing brown, granular staining are malignant prostate cells that express viral proteins. Source: Ila R. Singh, M.D., Ph.D., the University of Utah







“The problem with [the paper] is that when XMRV is so recent—XMRV evolved only between 1993 and 1996—it cannot possibly spread through virally in the human population,” researcher Hsing-Jien Kung from the University of California Davis Medical Center Cancer Center who has studied XMRV. “The reports show over 60% of the blood samples are positive in the CFS patients, that means this virus has spread wide and extensive and that is very, very unlikely, and I would say is impossible.”

Despite such criticism, lead author Judy Mikovits and her colleagues at the Whittemore Peterson Institute (WPI) stood behind their results. In October 2011, two of the 2009 paper’s authors retracted their contributions, and Mikovits was dismissed from her position at the WPI for not cooperating with other researchers at the institute. Soon after, the WPI filed a lawsuit against Mikovits, claiming that she stole notebooks and electronic equipment from the institute upon her dismissal, ultimately leading to her November 2011 arrest in California.

In other retraction news, the authors of a 2010 paper that supported the XMRV-CFS link no longer believe their conclusion in the face of the mounting evidence against it (3). In the original paper, published in the Proceedings of the National Academy of Sciences, a team led by Harvey J. Alter from the National Institutes of Health (NIH) reported the detection of MLV-related virus gene sequences in the blood of patients with CFS (4).

In their retraction, Alter’s team reported that while they replicated the findings themselves, there weren’t enough patient samples to distribute to other labs for independent verification. Furthermore, considering the numerous failed attempts to reproduce the findings that linked XMRV with CFS and their inability to isolate the virus by culture, a retraction was in order.

“The tool used is so easily contaminated and not necessarily because of bad hands, we have to recognize it’s a common happenstance in any laboratory,” Kung said. “In fact, I think we all have contamination problems and that’s nothing to be embarrassed about.”

In a 2011 study published in Science, Kung and researchers from Tufts University and the National Cancer Institute reported the recombinant origins of XMRV to explain the inconsistency in earlier experiments (5). In their experiment, the group found that human prostate cancer cell lines CWR22Rv1 and CWR-R1 and the progenitor human prostate tumor xenograft CWR22 were infected with XMRV, but the original CWR22 tumor was not. Specifically, they found the retroviruses PreXMRV-1 and PreXMRV-2 recombined to generate XMRV when CWR22 xenograft was passed in the mice.

With these two retractions, it seems like the evidence supporting the link between XMRV and CFS is diminishing.

“The viruses or the bacteria or other infection agents that may participate in causing prostate cancer are still unknown so it is a challenge that we continue to look for it without being discouraged by this particular incident,” said Kung. “This incident only says XMRV is not the agent; let’s not rule out other possibilities.”

References

1. Alberts, B. 2011. Retraction. Science 334:1636.

2. Lombardi, V.C., F.W. Ruscetti, J. Das Gupta, M.A. Pfost, K.S. Hagen, D.L. Peterson, S.K. Ruscetti, R.K. Bagni, C. Petrow-Sadowski, et al. 2009. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 326:585-9.

3. Lo, S., N. Pripuzova, B. Li, A.L. Komaroff, G. Hung, R. Wang R, and H.J. Alter. 2011. Retraction for Lo et al., Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. Proc Natl Acad Sci U S A 109:346.

4. Lo, S., N. Pripuzova, B. Li, A.L. Komaroff, G. Hung, R. Wang R, and H.J. Alter. 2010. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. Proc Natl Acad Sci 107: 15874-15879.

5. Paprotka, T., K.A. Delviks-Frankenberry, O. Cingöz, A. Martinez, H.J. Kung, C.G. Tepper, W.S. Hu, M.J. Fivash Jr, J.M. Coffin, and V.K. Pathak. 2011. Recombinant origin of the retrovirus XMRV. Science 333:97-101.

Keywords:  XMRV