Of Mice and Men: On the Origin of XMRV

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

Viruses in the reproductive tract: On their way to the germ line?

Studies of vertebrate genomes have indicated that all species contain in their chromosomes stretches of DNA with sequence similarity to viral genomes. How such ‘endogenous’ viral elements (EVEs) ended up in host genomes is usually explained in general terms such as ‘they entered the germ line at some point during evolution’. This seems a correct statement, but is also rather imprecise. The vast number of endogenous viral sequences suggest that common routes to the ‘germ line’ may exist, as relying on chance alone may not easily explain the abundance of EVEs in modern mammalian genomes. An increasing number of virus types have been detected in human semen and a growing number of studies have reported on viral infections that cause male infertility or subfertility and on viral infections that threaten in vitro fertilisation practices. Thus, it is timely to survey the pathway(s) that viruses can use to gain access to the human germ line. Embryo transfer and semen quality studies in livestock form another source of relevant information because virus infection during reproduction is clearly unwanted, as is the case for the human situation. In this review, studies on viruses in the male and female reproductive tract and in the early embryo will be discussed to propose a plausible viral route to the mammalian germ line