Recombinant origin of the retrovirus XMRV

Tobias Paprotka, Krista A. Delviks-Frankenberry, Oya Cingöz, Anthony Martinez, Hsing Jien Kung, Clifford G. Tepper, Wei Shau Hu, Matthew J. Fivash, John M. Coffin, Vinay K. Pathak

Research output: Contribution to journalArticle

192 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)97-101
Number of pages5
JournalScience
Volume333
Issue number6038
DOIs
Publication statusPublished - Jul 1 2011
Externally publishedYes

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Xenotropic murine leukemia virus-related virus
Retroviridae
Proviruses
Heterografts
Genetic Recombination
Prostate
Neoplasms
Viruses
Cell Line
Chronic Fatigue Syndrome
Virus Diseases
Prostatic Neoplasms
Genome

ASJC Scopus subject areas

  • General

Cite this

Paprotka, T., Delviks-Frankenberry, K. A., Cingöz, O., Martinez, A., Kung, H. J., Tepper, C. G., ... Pathak, V. K. (2011). Recombinant origin of the retrovirus XMRV. Science, 333(6038), 97-101. https://doi.org/10.1126/science.1205292

Recombinant origin of the retrovirus XMRV. / Paprotka, Tobias; Delviks-Frankenberry, Krista A.; Cingöz, Oya; Martinez, Anthony; Kung, Hsing Jien; Tepper, Clifford G.; Hu, Wei Shau; Fivash, Matthew J.; Coffin, John M.; Pathak, Vinay K.

In: Science, Vol. 333, No. 6038, 01.07.2011, p. 97-101.

Research output: Contribution to journalArticle

Paprotka, T, Delviks-Frankenberry, KA, Cingöz, O, Martinez, A, Kung, HJ, Tepper, CG, Hu, WS, Fivash, MJ, Coffin, JM & Pathak, VK 2011, 'Recombinant origin of the retrovirus XMRV', Science, vol. 333, no. 6038, pp. 97-101. https://doi.org/10.1126/science.1205292
Paprotka T, Delviks-Frankenberry KA, Cingöz O, Martinez A, Kung HJ, Tepper CG et al. Recombinant origin of the retrovirus XMRV. Science. 2011 Jul 1;333(6038):97-101. https://doi.org/10.1126/science.1205292
Paprotka, Tobias ; Delviks-Frankenberry, Krista A. ; Cingöz, Oya ; Martinez, Anthony ; Kung, Hsing Jien ; Tepper, Clifford G. ; Hu, Wei Shau ; Fivash, Matthew J. ; Coffin, John M. ; Pathak, Vinay K. / Recombinant origin of the retrovirus XMRV. In: Science. 2011 ; Vol. 333, No. 6038. pp. 97-101.
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