Title

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

Document Type

Article

Publication Date

2009

Keywords

Chromosome-Mapping, Herpesviridae-Infections, Immunity-Innate, Killer-Cells-Natural, Mice, Mice-Inbred-C57BL, Mice-Inbred-NZB, Muromegalovirus, Quantitative-Trait-Loci, Rodent-Diseases, Sex-Characteristics, X-Chromosome

JAX Source

Mamm Genome 2009 Jul; 20(7):414-23.

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.