Abstract
The novel human retrovirus xenotropic murine leukemia virus-related virus (XMRV) is arguably the most controversial virus of this moment. After its original discovery in prostate cancer tissue from North American patients, it was subsequently detected in individuals with chronic fatigue syndrome from the same continent. However, most other research groups, mainly from Europe, reported negative results. The positive results could possibly be attributed to contamination with mouse products in a number of cases, as XMRV is nearly identical in nucleotide sequence to endogenous retroviruses in the mouse genome. But the detection of integrated XMRV proviruses in prostate cancer tissue proves it to be a genuine virus that replicates in human cells, leaving the question: how did XMRV enter the human population? We will discuss two possible routes: either via direct virus transmission from mouse to human, as repeatedly seen for, e.g., Hantaviruses, or via the use of mouse-related products by humans, including vaccines. We hypothesize that mouse cells or human cell lines used for vaccine production could have been contaminated with a replicating variant of the XMRV precursors encoded by the mouse genome.
Highlights
The xenotropic murine leukemia virus-related virus (XMRV) is undoubtedly the most controversial human virus since its first detection in human samples in 2006 (Urisman et al, 2006)
Blasting whole genome XMRV sequences recovers very similar sequences with large stretches of sequence identity on mouse chromosomes 4, 5, 13, and Y, especially for the 3′ end of the XMRV genome. These results suggest that the genome of human XMRV is present, albeit in two parts, in the mouse genome with effectively no nucleotide changes
It is less likely that monoclonal antibodies from mice are a major source of XMRV in the human population as they are in use only recently, but they could provide a future supply of mouse-derived viruses
Summary
The xenotropic murine leukemia virus-related virus (XMRV) is undoubtedly the most controversial human virus since its first detection in human samples in 2006 (Urisman et al, 2006). The absence of other mousederived sequences, combined with the ease of infection of human cells with XMRV in vitro (Stieler et al, 2010), and the detection of integrated proviruses in prostate cancer tissues (Dong et al, 2007; Kim et al, 2008) indicated that laboratory contamination with mouse products is not a likely explanation for the origin of XMRV, at least for some of these studies. The human XPR1 receptor protein shows a preference for xenotropic retroviruses, but is able to mediate infection of polytropic murine leukemia retroviruses (P-MLV’s; Tailor et al, 1999). X-MLV’s cannot (re-)infect most of the laboratory mouse strains due to polymorphisms in the XPR1 protein that disable xenotropic virus entry (Marin et al, 1999). The XPR1 genotype that prohibits X-MLV entry was not found www.frontiersin.org van der Kuyl et al
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