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 × NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F2 crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F2 males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.
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Acknowledgments
This work was supported by NIH grants AI050072 (MGB), AR045222 (S.M. Fu and MGB), GM070683 (GC and QL). M. Rodriguez received support from an NIH Research Supplement to Promote Diversity (AI050072-06S1). We thank Drs. Victor Engelhard, Marcia McDuffie, Shu Man Fu, and Skip Virgin and members of the Brown lab for helpful discussion and comments on the manuscript. We also thank Dr. Mark Conway for expert statistical analyses.
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Rodriguez, M.R., Lundgren, A., Sabastian, P. et al. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice. Mamm Genome 20, 414–423 (2009). https://doi.org/10.1007/s00335-009-9203-8
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DOI: https://doi.org/10.1007/s00335-009-9203-8