Characterization, Mapping and Distribution of the Two XMRV Parental Proviruses

[Jemal]

Oya Cingz1, Tobias Paprotka2, Krista A. Delviks-Frankenberry2, Sheryl Wildt4, Wei-Shau Hu3, Vinay K. Pathak2, and John M. Coffin1,*
1 Department of Molecular Biology and Microbiology, Genetics Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA
2 Viral Mutation Section
3 Viral Recombination Section HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA
4 Harlan Laboratories, Indianapolis, IN 46250, USA

Xenotropic murine leukemia virus-related virus (XMRV) was previously reported to be associated with human prostate cancer and chronic fatigue syndrome. Our groups recently showed that XMRV was created through recombination between two endogenous murine retroviruses, PreXMRV-1 and PreXMRV-2, during the passaging of a prostate tumor xenograft in nude mice. Here, multiple approaches that led to the identification of PreXMRV-2, as well as the distribution of both parental proviruses among different mouse species are described. The chromosomal loci of both proviruses were determined in the mouse genome, and integration site information was used to analyze the distribution of both proviruses in 48 laboratory mouse strains and 46 wild-derived strains. The strain distribution of PreXMRV-1 and PreXMRV-2 are quite different, the former being found predominantly in Asian mice and the latter in European mice, making it unlikely that the two XMRV ancestors could have recombined independently in the wild to generate an infectious virus. XMRV was not present in any of the mouse strains tested, and among the wild-derived mouse strains analyzed, not a single mouse carried both parental proviruses. Interestingly, PreXMRV-1 and PreXMRV-2 were found together in three laboratory strains, Hsd nude, NU/NU and C57BR/cd, consistent with previous data that the recombination event that led to the generation of XMRV could only have occurred in the laboratory. The three laboratory strains carried the Xpr1n receptor variant non-permissive to XMRV and X-MLV infection, suggesting that the xenografted human tumor cells were required for the resulting XMRV recombinant to infect and propagate.

http://jvi.asm.org/cgi/content/short/JVI.06022-11v1

 

[Bob]

Well, it's an interesting theory, and it seems plausible to a lay person (me).

But I wonder if they've read the unpublished recombination paper that rebutts their previous and current conclusions:

Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns
Mattia C F Prosperi , William M Switzer, Walid Heneine and Marco Salemi
6 June 2011
Unpublished abstract presented to the '15th International Conference on Human Retroviruses: HTLV and Related Viruses'
Retrovirology 2011, 8(Suppl 1):A235doi:10.1186/1742-4690-8-S1-A235
http://www.retrovirology.com/content/8/S1/A235
Conclusion:
"Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution ... These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time."