To try to resolve the degree of association between XMRV and human disease, Pathak, who led these studies at NCI in its Viral Mutation Section, Coffin, and their colleagues examined human prostate cancer cells which contained XMRV, as well as the tumors from which these prostate cell specimens arose after they were grafted into mice. Grafting human tumors, called xenografts, into mice is a common way to study disease when it might be unsafe to test new treatments or methods in humans.
Upon careful examination in this new study, it was shown that initial prostate tumor xenografts did not contain XMRV but later tumors that had been derived from them did, demonstrating that XMRV was not present in the original human tumor as previously supposed. Instead, the virus appears to have infected tumor cells while they were in mice. In addition, the mice that were used for xenografting the prostate tumor cells contained two previously undescribed viruses, PreXMRV‐1 and PreXMRV‐2. Each of these viruses has a stretch of over 3,200 nucleotides, the basic building blocks of DNA, which is nearly identical to XMRV, differing by only a single nucleotide.
Genetic comparison of the PreXMRV‐1 and PreXMRV‐2 sequences revealed that each one has non-overlapping stretches that are nearly identical to XMRV. Pathak, Coffin, and their colleagues postulate that recombination between these viruses generated XMRV in human cells while the cells were being grown in a mouse sometime between 1993 and1996 and infected the prostate tumor cells. Recombination between virus genomes in a cell infected by more than one virus is common.
Based on this genetic analysis, the scientists concluded that XMRV was not present in the original prostate tumor samples but arose only after they had been put into mice. The probabi
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