‘Recombinant Origin of the Retrovirus XMRV’, Science Express, 31 May 2011

From ‘Science Express’, 31 May 2011

Tobias Paprotka1,*, Krista A. Delviks-Frankenberry1,*, Oya Cingöz3,4,*, Anthony Martinez5, Hsing-Jien Kung5,6, Clifford G. Tepper5, Wei-Shau Hu2, Matthew J. Fivash Jr.7, John M. Coffin3,4, and Vinay K. Pathak1,†
+ Author Affiliations

1Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
2Viral Recombination Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
3Department of Molecular Biology and Microbiology, School of Medicine, Tufts University, 150 Harrison Avenue, Boston, MA 02111, USA.
4Genetics Program, School of Medicine, Tufts University, 150 Harrison Avenue, Boston, MA 02111, USA.
5Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA.
6Department of Urology, University of California, Davis, Sacramento, CA 95817, USA.
7Data Management Services, Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA.
†↵To whom correspondence should be addressed. E-mail: vinay.pathak@nih.gov
↵* These authors contributed equally to this work.

ABSTRACT

The retrovirus XMRV (xenotropic murine leukemia virus–related virus) has been detected in human prostate tumors and in blood samples from patients with chronic fatigue syndrome, but these findings have not been replicated. We hypothesized that an understanding of when and how XMRV first arose might help explain the discrepant results. We studied human prostate cancer cell lines CWR22Rv1 and CWR-R1, which produce XMRV virtually identical to the viruses recently found in patient samples, as well as their progenitor human prostate tumor xenograft (CWR22) that had been passaged in mice. We detected XMRV infection in the two cell lines and in the later passage xenografts, but not in the early passages. In particular, we found that the host mice contained two proviruses, PreXMRV-1 and PreXMRV-2, which share 99.92% identity with XMRV over >3.2-kilobase stretches of their genomes. We conclude that XMRV was not present in the original CWR22 tumor but was generated by recombination of two proviruses during tumor passaging in mice. The probability that an identical recombinant was generated independently is negligible (~10–12); our results suggest that the association of XMRV with human disease is due to contamination of human samples with virus originating from this recombination event.

Received for publication 1 February 2011.
Accepted for publication 5 May 2011.

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