Characterization, Mapping, and Distribution of the Two XMRV Parental Proviruses
Oya Cing?za,
Tobias Paprotkab,
Krista A. Delviks-Frankenberryb,
Sheryl Wildtd,
Wei-Shau Huc,
Vinay K. Pathakb and
John M. Coffina
- Author Affiliations
aDepartment of Molecular Biology and Microbiology, Genetics Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA
bViral Mutation Section
cViral Recombination Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, USA
dHarlan Laboratories, Indianapolis, Indiana, USA
ABSTRACT
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 distributions 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 have occurred only in the laboratory. The three laboratory strains carried the Xpr1n receptor variant nonpermissive to XMRV and xenotropic murine leukemia virus (X-MLV) infection, suggesting that the xenografted human tumor cells were required for the resulting XMRV recombinant to infect and propagate.
FOOTNOTES
Received 15 August 2011.
Accepted 26 September 2011.
Published ahead of print 26 October 2011
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
