Endogenous gammaretrovirus acquisition in Mus musculus subspecies carrying functional variants of the XPR1 virus receptor

J Virol. 2013 Sep;87(17):9845-55. doi: 10.1128/JVI.01264-13. Epub 2013 Jul 3.


The xenotropic and polytropic mouse leukemia viruses (X-MLVs and P-MLVs, respectively) have different host ranges but use the same functionally polymorphic receptor, XPR1, for entry. Endogenous retroviruses (ERVs) of these 2 gammaretrovirus subtypes are largely segregated in different house mouse subspecies, but both MLV types are found in the classical strains of laboratory mice, which are genetic mosaics of 3 wild mouse subspecies. To describe the subspecies origins of laboratory mouse XP-MLV ERVs and their coevolutionary trajectory with their XPR1 receptor, we screened the house mouse subspecies for known and novel Xpr1 variants and for the individual full-length XP-MLV ERVs found in the sequenced C57BL mouse genome. The 12 X-MLV ERVs predate the origins of laboratory mice; they were all traced to Japanese wild mice and are embedded in the 5% of the laboratory mouse genome derived from the Asian Mus musculus musculus and, in one case, in the <1% derived from M. m. castaneus. While all 31 P-MLV ERVs map to the 95% of the laboratory mouse genome derived from P-MLV-infected M. m. domesticus, no C57BL P-MLV ERVs were found in wild M. m. domesticus. All M. m. domesticus mice carry the fully permissive XPR1 receptor allele, but all of the various restrictive XPR1 receptors, including the X-MLV-restricting laboratory mouse Xpr1(n) and a novel M. m. castaneus allele, originated in X-MLV-infected Asian mice. Thus, P-MLV ERVs show more insertional polymorphism than X-MLVs, and these differences in ERV acquisition and fixation are linked to subspecies-specific and functionally distinct XPR1 receptor variants.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Alleles
  • Animals
  • Animals, Wild / genetics
  • Animals, Wild / virology
  • Endogenous Retroviruses / isolation & purification
  • Endogenous Retroviruses / physiology*
  • Evolution, Molecular
  • Genetic Variation
  • Host Specificity / genetics*
  • Host Specificity / physiology*
  • Leukemia Virus, Murine / isolation & purification
  • Leukemia Virus, Murine / physiology*
  • Mice / classification
  • Mice / genetics*
  • Mice / virology*
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Proviruses / isolation & purification
  • Proviruses / physiology
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Virus / genetics*
  • Receptors, Virus / physiology*
  • Species Specificity
  • Terminal Repeat Sequences
  • Xenotropic and Polytropic Retrovirus Receptor


  • Receptors, G-Protein-Coupled
  • Receptors, Virus
  • Xenotropic and Polytropic Retrovirus Receptor
  • Xpr1 protein, mouse