Article

Mammalian Genome

, Volume 20, Issue 7, pp 414-423

First online:

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

  • Marisela R. RodriguezAffiliated withDepartment of Microbiology, University of Virginia School of MedicineDepartment of Internal Medicine, Division of Rheumatology, Washington University in St. Louis Medical Center Email author 
  • , Alyssa LundgrenAffiliated withDepartment of Microbiology, University of Virginia School of Medicine
  • , Pearl SabastianAffiliated withDepartment of Microbiology, University of Virginia School of Medicine
  • , Qian LiAffiliated withThe Jackson Laboratory
  • , Gary ChurchillAffiliated withThe Jackson Laboratory
  • , Michael G. BrownAffiliated withDepartment of Microbiology, University of Virginia School of MedicineDepartment of Medicine, University of Virginia School of Medicine

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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 × NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F2 crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F2 males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.