Abstract
Ly49H(+) NK cells play a critical role in innate antiviral immune responses to murine CMV (MCMV). Ly49H(b6) recognition of MCMV-encoded m157 on infected cells activates natural killing required for host resistance. We show that mAb 3D10 (anti-Ly49H) recognizes comparable subsets of NK cells from New Zealand White (NZW), New Zealand Black (NZB), and C57BL/6 spleens. However, virus levels in the spleens of MCMV-infected NZW and NZB mice differed greatly. We found that MCMV replication in infected NZW spleens was limited through NK cells. Alternately, NZB mice were profoundly susceptible to MCMV infection. Although 3D10 mAb injections given before infection interfere with Cmv1-type resistance in C57BL/6 mice, similar mAb injections did not affect NZW resistance, likely because NZW NK cell receptors did not bind MCMV-encoded m157. Instead, anti-MCMV host defenses in hybrid NZ offspring were associated with multiple chromosome locations including several putative quantitative trait loci that did not overlap with H-2 or NK gene complex loci. This study revealed a novel pathway used by NK cells to defend against MCMV infection. Thus, the importance of Ly49H in MCMV infection may be shaped by other additional background genes.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Animals
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Antigens, Ly / biosynthesis
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Antigens, Ly / genetics
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Antigens, Ly / physiology*
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Antigens, Surface / biosynthesis
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Antigens, Surface / genetics
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Cell Line
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Cytotoxicity, Immunologic / genetics
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Genetic Markers
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Genetic Predisposition to Disease
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Herpesviridae Infections / genetics
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Herpesviridae Infections / immunology*
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Herpesviridae Infections / prevention & control*
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Humans
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Hybridomas
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Immunity, Innate / genetics
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism*
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Killer Cells, Natural / virology
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Lectins, C-Type / biosynthesis
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Lectins, C-Type / genetics
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Lymphocyte Activation / genetics
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Lymphocyte Depletion
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred NZB
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Muromegalovirus / genetics
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Muromegalovirus / immunology*
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NIH 3T3 Cells
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NK Cell Lectin-Like Receptor Subfamily A
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NK Cell Lectin-Like Receptor Subfamily B
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / genetics
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Receptors, Immunologic / physiology
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Receptors, NK Cell Lectin-Like
Substances
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Antigens, Ly
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Antigens, Surface
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Genetic Markers
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KLRB1 protein, human
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Klra8 protein, mouse
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Lectins, C-Type
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NK Cell Lectin-Like Receptor Subfamily A
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NK Cell Lectin-Like Receptor Subfamily B
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Receptors, Immunologic
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Receptors, NK Cell Lectin-Like