Escape variants of the XPR1 gammaretrovirus receptor are rare due to reliance on a splice donor site and a short hypervariable loop

Virology. 2014 Nov:468-470:63-71. doi: 10.1016/j.virol.2014.07.049. Epub 2014 Aug 20.

Abstract

Entry determinants in the XPR1 receptor for the xenotropic/polytropic mouse leukemia viruses (XP-MLVs) lie in its third and fourth putative extracellular loops (ECLs). The critical ECL3 receptor determinant overlies a splice donor and is evolutionarily conserved in vertebrate XPR1 genes; 2 of the 3 rare replacement mutations at this site destroy this receptor determinant. The 13 residue ECL4 is hypervariable, and replacement mutations carrying an intact ECL3 site alter but do not abolish receptor activity, including replacement of the entire loop with that of a jellyfish (Cnidaria) XPR1. Because ECL4 deletions are found in all X-MLV-infected Mus subspecies, we deleted each ECL4 residue to determine if deletion-associated restriction is residue-specific or is effected by loop size. All deletions influence receptor function, although different deletions affect different XP-MLVs. Thus, receptor usage of a constrained splice site and a loop that tolerates mutations severely limits the likelihood of host escape mutations.

Keywords: Retrovirus entry; Retrovirus evolution; Retrovirus restriction genes; XPR1 gammaretrovirus receptor; Xenotropic/polytropic gammaretroviruses.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Gammaretrovirus / physiology*
  • Genetic Variation
  • Mice
  • RNA Splice Sites
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Scyphozoa
  • Virus Internalization
  • Xenotropic and Polytropic Retrovirus Receptor

Substances

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