A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.
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.
Rodriguez
Marisela R
MR
Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. mrrodrig@im.wustl.edu
Lundgren
Alyssa
A
Sabastian
Pearl
P
Li
Qian
Q
Churchill
Gary
G
Brown
Michael G
MG
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice / Q000235:genetics* / Q000276:immunology / Q000821:virology; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology; D040641:Quantitative Trait Loci; D012376:Rodent Diseases / Q000235:genetics* / Q000276:immunology; D012727:Sex Characteristics; D014960:X Chromosome / Q000235:genetics*