Characterization, mapping, and distribution of the two XMRV parental proviruses.
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 Xpr1(n) 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.
Department of Molecular Biology and Microbiology, Genetics Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.
Oya
O
Cingöz
Tobias
T
Paprotka
Krista A
KA
Delviks-Frankenberry
Sheryl
S
Wildt
Wei-Shau
WS
Hu
Vinay K
VK
Pathak
John M
JM
Coffin
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics / Q000821:virology*; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics; D011995:Recombination, Genetic; D012192:Retroviridae Infections / Q000662:veterinary* / Q000821:virology; D016415:Sequence Alignment; D016662:Virus Integration; D000089842:Xenotropic and Polytropic Retrovirus Receptor; D058008:Xenotropic murine leukemia virus-related virus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology
D011991:Receptors, Virus; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor; C000715268:Xpr1 protein, mouse