XMRV and CFS; the sad end of a story

Kuppeveld Frank van

In a Comment published by The Lancet, Frank van Kuppeveld and Jos van der Meer review the recent events on the proposed role of the xenotropic murine leukaemia virus (MLV)-related virus (XMRV) in chronic fatigue syndrome (CFS).

In 2009, in Science, Lombardi et al. described the occurrence of XMRV, a retrovirus, in PBMC in 67% of patients with CFS and in 3.7% of healthy controls. This paper was presented as a breakthrough with important implications for prevention and treatment of CFS as well as for transfusion practices. Furthermore, it gave new hope to CFS patients who are seeking a cause for their suffering, and some of them already starting using antiretroviral drugs.

However, the observations of Lombardi et al. were questioned by 3 independent studies, including one from Nijmegen (van Kuppeveld et al., BMJ, 2010), that failed to XMRV in CFS patients and controls. The discrepancy in the results provoked a hot debate and researchers unable to confirm the results of the Science paper were accused of bad science.

In the mean time, many more studies failed to detect XMRV in CFS patients and controls. Now, 3 new publications - 2 of which are published in Science - seem to provide the final nail in the coffin of the XMRV-CFS story. Two papers provide convincing evidence that the association of XMRV with CFS is due to contamination of laboratory reagents with XMRV- and MLV-containing mouse DNA. The third shows that XMRV is not a genuine human pathogen but a spectacular laboratory artifact produced by recombination of 2 mouse proviruses during recent passage of a human xenograft in mice.

Based on this evidence, editors of Science have asked the authors of the Lombardi et al. paper to voluntarily retract the paper. However, the authors of this publication have declared that "it is premature to retract our paper". Hence, Science has now published an Editorial Expression of Concern about the Lombardi et al. paper. Sadly, we have to conclude that the world witnessed another false claim that gave new hope to CFS patients.

XMRV and CFS; the sad end of a story. Frank JM van Kuppeveld and Jos WM van der Meer. Early Online Publication, 21 June 2011. DOI:10.016/S0140-6736(11)60899-4.

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