Immunogenetics

, Volume 61, Issue 11–12, pp 755–764

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

  • Michael D. Stadnisky
  • Ani Manichaikul
  • Alyssa G. Lundgren
  • Michael G. Brown
Original Article

Abstract

An H-2k MHC locus is critical for murine cytomegalovirus (MCMV) resistance in MA/My mice and virus control is abolished if H-2k is replaced with H-2b MHC genes from MCMV-susceptible C57L mice. Yet, H-2k 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 × MA/My) and (MA/My × C57L) F2 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-2k MHC QTL to mitigate spleen MCMV levels. We provide biological confirmation that this chromosome 6 QTL provided MCMV control independent of H-2k via NK cells. Importantly, both chromosome 6 and 19 QTLs contribute to virus control independent of H-2k. Altogether, MHC and non-MHC MCMV-resistance QTL contribute in early resistance to MCMV infection in this genetic system.

Keywords

Mouse QTL MHC Cytomegalovirus 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Michael D. Stadnisky
    • 1
  • Ani Manichaikul
    • 2
    • 3
  • Alyssa G. Lundgren
    • 4
  • Michael G. Brown
    • 1
    • 4
    • 5
    • 6
  1. 1.Department of MicrobiologyUniversity of Virginia School of MedicineCharlottesvilleUSA
  2. 2.Center for Public Health GenomicsUniversity of Virginia School of MedicineCharlottesvilleUSA
  3. 3.Department of Public Health Sciences, Division of Biostatistics and EpidemiologyUniversity of Virginia School of MedicineCharlottesvilleUSA
  4. 4.Department of Medicine, Division of NephrologyUniversity of Virginia School of MedicineCharlottesvilleUSA
  5. 5.Beirne B. Carter Center for Immunology ResearchUniversity of Virginia School of MedicineCharlottesvilleUSA
  6. 6.Department of Medicine, Beirne B. Carter Center for Immunology ResearchUniversity of Virginia Health SystemCharlottesvilleUSA

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