NK gene complex and chromosome 19 loci enhance MHC resistance to murine cytomegalovirus infection.
An H-2(k) MHC locus is critical for murine cytomegalovirus (MCMV) resistance in MA/My mice and virus control is abolished if H-2(k) is replaced with H-2(b) MHC genes from MCMV-susceptible C57L mice. Yet, H-2(k) resistance varies with genetic background; thus, modifiers of virus resistance must exist. To identify non-MHC resistance loci, spleen and liver MCMV levels and genome-wide genotypes were assessed in (C57L x MA/My) and (MA/My x C57L) F(2) offspring (representing 550 meioses). Significantly, a non-Mendelian frequency of MHC genotypes was observed for offspring of the latter cross. Quantitative trait loci (QTL) and their interaction potential in MCMV resistance were assessed in R/qtl; QTL on chromosomes 17, 6, and 19 affected MCMV levels in infected animals. A chromosome 6 QTL was linked with the NK gene complex and acted in an additive fashion with an H-2(k) MHC QTL to mitigate spleen MCMV levels. We provide biological confirmation that this chromosome 6 QTL provided MCMV control independent of H-2(k) via NK cells. Importantly, both chromosome 6 and 19 QTLs contribute to virus control independent of H-2(k). Altogether, MHC and non-MHC MCMV-resistance QTL contribute in early resistance to MCMV infection in this genetic system.
Stadnisky
Michael D
MD
Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Manichaikul
Ani
A
Lundgren
Alyssa G
AG
Brown
Michael G
MG
D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D005260:Female; D055106:Genome-Wide Association Study; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008099:Liver / Q000378:metabolism / Q000821:virology; D008126:Lod Score; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*; D040641:Quantitative Trait Loci / Q000235:genetics; D013154:Spleen / Q000378:metabolism / Q000821:virology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D006649:Histocompatibility Antigens