Recombination Origin of Retrovirus XMRV

Two proviruses, PreXMRV-1 and PreXMRV-2,  share 99.92 percent identity with XMRV over 3200-base stretches of their genomes, and recombine to make a consensus XMRV sequence about 6500 bases in length.

Two proviruses, PreXMRV-1 and PreXMRV-2, share 99.92 percent identity with XMRV over 3200-base stretches of their genomes, and recombine to make a consensus XMRV sequence about 6500 bases in length.

Xenotropic murine leukemia virus–related virus (XMRV) was first reported in samples from a human prostate tumor in 2006, and, at that time, claims were made that XMRV infection rates ranged from 6 to 27 percent of human prostate cancers.  Later research reported XMRV in the blood of 67 percent of people with chronic fatigue syndrome (CFS). When follow-up studies failed to detect XMRV in multiple sets of specimens from people with prostate cancer or CFS and healthy controls, the original reports came under closer scrutiny.

To try to resolve the association, if any, between XMRV and human disease, CCR’s researchers  Tobias Paprotka, Ph.D., Krista Delviks-Frankenberry, Ph.D. and Vinay Pathak, Ph.D., Chief of the Viral Mutation Section of NCI’s HIV Drug Resistance Program teamed up with co-authors Oya Cingöz and John Coffin, Ph.D., special advisor to the NCI director, and professor at Tufts University School of Medicine.

The researchers discovered and reported in Science that the human prostate cancer xenograft CWR22 and derived cell lines CWR22Rv1 and CWR-R1 harbor XMRV genomes almost identical to the viruses recently found in patient samples. While the Pathak team was able to detect XMRV infection in the two cell lines and in the later passage xenografts, they could not do so in the early passages. Things became clearer when they found that the host mice themselves contained two proviruses, PreXMRV-1 and PreXMRV-2, that share 99.92% identity with XMRV over 3200-base stretches of their genomes. So they concluded that XMRV was not present in the original prostate tumor xenograft (CWR22), but was generated by recombination of the two PreXMRVs , which infected  the xenograft during  passaging.

The probability of an identical recombinant being generated independently in another mouse is negligible (one in a trillion chances), so the Pathak team’s results suggest that all XMRVs reported to date originate from this event. 

Summary Posted: 12/2011

Reference

Recombinant origin of the retrovirus XMRV. Paprotka T, Delviks-Frankenberry KA, Cing&öz O, Martinez A, Kung HJ, Tepper CG, Hu WS, Fivash MJ Jr, Coffin JM, Pathak VK. Reviewed by Donna Kerrigan PubMed Link