Fodil-Cornu, Nassima and Loredo-Osti, J. Concepcion and Vidal, Silvia M. (2011) NK Cell Receptor/H2-Dk–Dependent Host Resistance to Viral Infection Is Quantitatively Modulated by H2q Inhibitory Signals. PLoS Genetics, 7 (4). pp. 1-13. ISSN 1553-7390
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The cytomegalovirus resistance locus Cmv3 has been linked to an epistatic interaction between two loci: a Natural Killer (NK) cell receptor gene and the major histocompatibility complex class I (MHC-I) locus. To demonstrate the interaction between Cmv3 and H2k, we generated double congenic mice between MA/My and BALB.K mice and an F2 cross between FVB/N (H-2q) and BALB.K (H2k) mice, two strains susceptible to mouse cytomegalovirus (MCMV). Only mice expressing H2k in conjunction with Cmv3MA/My or Cmv3FVB were resistant to MCMV infection. Subsequently, an F3 cross was carried out between transgenic FVB/H2-Dk and MHC-I deficient mice in which only the progeny expressing Cmv3FVB and a single H2-Dk class-I molecule completely controlled MCMV viral loads. This phenotype was shown to be NK cell–dependent and associated with subsequent NK cell proliferation. Finally, we demonstrated that a number of H2q alleles influence the expression level of H2q molecules, but not intrinsic functional properties of NK cells; viral loads, however, were quantitatively proportional to the number of H2q alleles. Our results support a model in which H-2q molecules convey Ly49-dependent inhibitory signals that interfere with the action of H2-Dk on NK cell activation against MCMV infection. Thus, the integration of activating and inhibitory signals emanating from various MHC-I/NK cell receptor interactions regulates NK cell–mediated control of viral load.
|Keywords:||Major histocompatibility antigen class 1, Natural killer cell receptor, Allele, Animal cell, Animal experiment, Animal model, Animal tissue, Article, Controlled study, Cytomegalovirus infection, Host resistance, In vivo study, Infection resistance, Infection sensitivity, Lymphocyte activation, Lymphocyte proliferation, Mouse, Natural killer cell, Nonhuman, Protein protein interaction, Virus immunity, Virus load, Cytomegalovirus, Maize chlorotic mottle virus, Mus|
|Department(s):||Science, Faculty of > Mathematics and Statistics|
|Date:||21 April 2011|
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