XMRV: Not a Mousy Virus

Abstract

The newly discovered mouse-derived human retrovirus, xenotropic murine leukemia virusrelated virus (XMRV), is currently fuelling both the scientific and public debate, where skeptics suggest that results are based on laboratory contamination, while the “believers” have already dressed the virus with highly pathogenic potential. Could the truth lie somewhere in the middle? XMRV was discovered in 2006 in tumor tissue from patients with prostate cancer,1 with a viral genome sequence highly similar to that of mouse xenotropic retroviruses. Sequence analysis suggested that XMRV is a novel recombinant derived from two fragmented endogenous murine viruses integrated in the mouse genome. XMRV was subsequently detected in other prostate cancer tissues and in blood from patients with CFS (chronic fatigue syndrome). However, most other studies failed to replicate these findings, especially outside the USA, suggesting either that the virus has a limited geographical spread, or that positive results were due to contamination of biological reagents or human samples with mouse DNA. Four recent papers indeed show that murine DNA sequences can be detected virtually everywhere,2−5 and that extreme care should be taken when amplifying XMRV sequences. These results certainly put into serious doubt some of the high prevalence results and proposed disease associations that could not be confirmed by others. However, these recent studies do not imply, and in fact did not intend to prove, that all positive results reported thus far are due to contamination, and that XMRV in humans can be dismissed as an artefact. The most important remaining question is: does XMRV infect and replicate in humans, in other words is it a genuine human virus apart from being an easy and frequent contaminant? The relevant subsequent questions would be: “how did XMRV end up in humans” and “is XMRV infection associated with disease”? It is of utmost importance to resolve these questions in a timely manner, as some CFS patients have begun taking antiretroviral drugs that can have side effects. Based on the original XMRV studies, it has also been proposed that CFS patients be banned from donating blood. The best evidence for XMRV replicating in human cells is the detection of proviral integrations flanked by human genome sequences in prostate tissue from eleven patients.6,7 The flanks are human and not mouse sequences, and the insertion sites differ for each clinical sample, thus ruling out a mouse-contamination and