NK gene complex and chromosome 19 loci enhance MHC resistance to murine cytomegalovirus infection

Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Immunogenetics (Impact Factor: 2.23). 10/2009; 61(11-12):755-64. DOI: 10.1007/s00251-009-0400-0
Source: PubMed


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.

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    • "However, comparisons of NK cells in NKC congenic mice (S3Fig), or C57L and M.H2 b mice (S4AFig) revealed similar sensitivity to ex vivo triggering via several different NK stimulatory receptors, and consequently no difference in NK cell licensing. Lower viral loads in NKC c57l than in NKC mamy spleens (Fig 2C and 2D, [31]), nonetheless prompted further analysis of G2 + NK cell reactivity to MCMV. In agreement with results from C57L-derived NKC congenic mice, lower G2 + NK cell percentages and G2 receptor MFI trends were observed in C57L mice, in comparison to MHCmatched , but NKC-disparate M.H2 b mice (S4BFig). "
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