Abstract
Peritoneal (PM) and bone marrow-derived (BMM) macrophages and lung fibroblasts (LF) from inbred, intra-H-2 recombinant, H-2 mutant, and hybrid mice were infected with murine cytomegalovirus (MCMV) under centrifugal enhancement. At the concentration of virus employed, peritoneal macrophages from strains carrying Kd, Kb, Dd, KS and/or Ds, K4 and/or D4 alleles could be infected to a level of 80%–100%, as assessed by viral antigen expression or loss of Fc receptors. Cells lacking these haplotypes and carrying Kk, Kf, Dk, Df, or Db were resistant, yielding levels of infection below 20% . The background (non-H-2) and class II genotype and the S allele did not influence the proportions of cells infected. Furthermore, sensitivity was dominant in the F, progeny of H-2 b x H-2 k and H-2d x H-2 k crosses, and was not compromised by thebm1, bm3, bm10, or bm14 mutations in the al orα2 regions of Kb orD b. The proportions of cells able to release infectious virus were low, but paralleled the frequencies of viral antigen expression. The class I genotype also determined susceptibility to MCMV infection in BMM and LF, although up to 35% of H-2 k BMM and 46% of H-2 k LF could be infected. The findings are consistent with an association between K and D antigens and a cellular receptor for MCMV on all three cell types.
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Allan, J. E. and Shellam, G. R.: Genetic control of murine cytomegalovirus infection: virus titres in resistant and susceptible strains of mice.Arch Virol 81: 139–150, 1984
Arnold, B., Burgert, H. G., Archibald, A. L., and Kvist, S.: Complete nucleotide sequence of the murine H-2k k gene. Comparison of three H-2K locus alleles.Nucleic Acids Res 12: 9473–9487, 1984
Dasgupta, J. D., Watkins, S., Slayter, H., and Yunis, E. J.: Receptorlike nature of Class I HLA: endocytosis via coated pits.J Immunol 141: 2577–2580, 1988
Dower, S. K. and Segal, D. M.: Interaction of monoclonal antibodies with MHC Class I antigens on mouse spleen cells. II. Levels of expression of H-2K, H-2D and H-2L in different mouse strains.J Immunol 134: 431–435, 1985
Emerson, S. G., Murphy, D. B., and Cole, R. E.: Selective turnover and shedding of H-2K and H-2D antigens is controlled by the major histocompatibility complex. Implications for H-2-restricted recognition.J Exp Med 152: 783–795, 1980
Glenn, J.: Cytomegalovirus infections following renal transplantation.Rev Infect Dis 3: 1151–1178, 1981
Grundy (Chalmer), J. E., Mackenzie, J. S., and Stanley, N. F.: The influence of H-2 and non H-2 genes on resistance to murine cytomegalovirus infection.Infect Immun 32: 227–286, 1981
Grundy, J. E., McKeating, J. A., Ward, P. J., Sanderson, A. R., and Griffiths, P. D.: β2 microglobulin enhances the infectivity of cytomegalovirus and when bound to the virus enables Class I HLA molecules to be used as a virus receptor.J Gen Virol 68: 793–803, 1987
Harnett, G. B. and Shellam, G. R.: Variation in murine cytomegalovirus replication in fibroblasts from different mouse strains in vitro: correlation with in vivo resistance.J Gen Virol 62: 39–47, 1982
Hayashi, K., Saze, K., and Uchida, Y.: Studies of latent cytomegalovirus infection: the macrophage as a virus-harboring cell.Microbiol Immunol 29: 625–634, 1985
Hochman, J. H., Shimizu, Y., De Mars, R., and Edidin, M.: Specific associations of fluorescentβ-2-microglobulin with cell surfaces. The affinity of different H-2 and HLA antigens for β-2-microglobulin.J Immunol 140: 2322–2329, 1988
Hodgkin, P. D., Scalzo, A. A., Swaminathan, N., Price, P., and Shellam, G. R.: Murine cytomegalovirus binds reversibly to mouse embryo fibroblasts: implications for quantitation and explanation of centrifugal enhancement.J Virol Methods 22: 215–230, 1988
Holt, P. G., Degebrodt, A., Venaille, T., O'Leary, C., Krska, K., Flexman, J., Farrell, H. E., Shellam, G., Young, P., Penhale, J., Robertson, T. A., and Papadimitriou, J. M.: Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays.Immunology 54: 139–147, 1985
Huet, C., Ash, J. F., and Singer, S. J.: The antibody-induced clustering and endocytosis of HLA antigens on cultured human fibroblasts.Cell 21: 429–438, 1980
Lawson, C. M., O'Donoghue, H., Bartholomaeus, W. N., and Reed, W. D.: Genetic control of cytomegalovirus induced myocarditis.Immunology 69: 20–26, 1990
Le, A. V. and Doyle, D.: N-linked oligosaccharides of the H-2Dk histocompatibility protein heavy chain influence its transport and cellular distribution.Biochemistry 24: 6238–6245, 1985
Maloy, W. L., Lew, A. M., Anderson, R. W., and Coligan, J. E.: H-2K molecules have two different C-termini, one of which is K-region specific.Mol Immunol 25: 453–463, 1988
Mercer, J. A., Wiley, C. A., and Spector, D. H.: Pathogenesis of murine cytomegalovirus infection: identification of infected cells in the spleen during acute and latent infections.J Virol 62: 987–997, 1988
Michaelson, J.: Genetic polymorphism of 02-microglobulin (β2m) maps to the H-3 region of chromosome 2.Immunogenetics 13: 167–171, 1981
Muller, M. T. and Hudson, J. B.: Cell cycle dependency of murine cytomegalovirus in synchronized 3T3 cells.J Virol 22: 267–272, 1977
O'Neill, H. C. and Blanden, R. V.:Quantitative differences in the expression of parentally-derived H-2 antigens in F, hybrid mice affect T cell responses.J Exp Med 149: 724–731, 1979
O'Neill, H. C. and McKenzie, I. F. C.: Quantitative variation in H-2-antigen expression. I. Estimation of H-2K and H-2D expression in different strains of mice.Immunogenetics 11: 225–239, 1980
Ozato, K., Takahashi, H., Appella, E., Sears, D. W., Murre, C., Seidman, J. G., Kimura, S., and Tada, N.: Polymorphism of murine major-histocompatibility class I antigen: assignment of putative allodeterminants to distinct positions of the amino acid sequence within the first external domain of the antigen.J Immunol 134: 1749–1757, 1985
Price, P., Winter, J. G., and Shellam, G. R.: Genetically-determined resistance to murine cytomegalovirus: a role for lymphocytostatic macrophages.J Gen Virol 68: 2997–3009, 1987a
Price, P., Winter, J. G., Nikoletti, S., Hudson, J. B., and Shellam, G. R.: Functional changes in murine macrophages infected with cytomegalovirus relate to H-2-determined sensitivity to infection.J Virol 61: 3602–3606, 1987b
Schmidt, W., Festenstein, H., Ward, P. J., and Sanderson, A. R.: Interspecies exchange of 02-microglobulin and associated MHC and differential antigens.Immunogenetics 13: 483–491, 1981
Shanley, J. D.: Host genetic factors influence murine cytomegalovirus lung infection and interstitial pneumonitis.J Gen Virol 65: 2121–2128, 1984
Stanley, E. R. and Heard, P. M.: Factors regulating macrophage production and growth. Purification and some properties of the colony stimulating factor from medium conditioned by mouse L cells.J Biol Chem 252: 4305–4312, 1977
Stannard, L. M.: 02-Microglobulin binds to the tegument of cytomegalovirus: an immunogold study.J Gen Virol 70: 2179–2184, 1989
Stephan, D., Sun, H., Fischer Lindahl, K., Meyer, E., Hamerling, G., Hood, L., and Steinmetz, M.: Organization and evolution of D region class I genes in the mouse major histocompatibility complex.J Exp Med 163: 1227–1244, 1986
Van Bruggen, I., Price, P., Robertson, T. A., and Papadimitriou, J. M.: Morphological and functional changes during cytomegalovirus replication in murine macrophages.J Leuk Biol 46: 508–520, 1989
Wood, P. R., Simes, R. J., and Nelson, D. S.: Activity of mouse macrophages purified by adherence to, and removal from, a plastic surface.J Immunol Methods 28: 117–125, 1979
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Price, P., Gibbons, A.E. & Shellam, G.R. H-2 class I loci determine sensitivity to MCMV in macrophages and fibroblasts. Immunogenetics 32, 20–26 (1990). https://doi.org/10.1007/BF01787324
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DOI: https://doi.org/10.1007/BF01787324