title: Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection.
abstract: The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen.
authors: Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.|Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Alyssa Lundgren
authors: AL
authors: Gillespie
authors: Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Jeffrey
authors: J
authors: Teoh
authors: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Heather
authors: H
authors: Lee
authors: Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.|Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Jessica
authors: J
authors: Prince
authors: Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Michael D
authors: MD
authors: Stadnisky
authors: Department of Pathology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Monique
authors: M
authors: Anderson
authors: Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: William
authors: W
authors: Nash
authors: Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Pathology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Claudia
authors: C
authors: Rival
authors: Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.|Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Hairong
authors: H
authors: Wei
authors: Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Awndre
authors: A
authors: Gamache
authors: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States of America.|Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Charles R
authors: CR
authors: Farber
authors: Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Pathology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Kenneth
authors: K
authors: Tung
authors: Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.|Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America.|Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Michael G
authors: MG
authors: Brown
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics* / Q000276:immunology; D056426:Genetic Loci; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: C083041:D(kappa) (62-85) peptide; D015395:Histocompatibility Antigens Class I; C452844:Ly49G2 receptor; D011971:Receptors, Immunologic