A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice

Mamm Genome. 2009 Jul;20(7):414-23. doi: 10.1007/s00335-009-9203-8. Epub 2009 Jul 30.

Abstract

NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

Publication types

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

MeSH terms

  • Animals
  • Chromosome Mapping
  • Female
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / veterinary*
  • Immunity, Innate*
  • Killer Cells, Natural / immunology
  • Male
  • Mice / genetics*
  • Mice / immunology
  • Mice / virology
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Muromegalovirus / immunology*
  • Muromegalovirus / physiology
  • Quantitative Trait Loci*
  • Rodent Diseases / genetics*
  • Rodent Diseases / immunology
  • Sex Characteristics
  • X Chromosome / genetics*