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H-2 class I loci determine sensitivity to MCMV in macrophages and fibroblasts
P Price1, A E Gibbons, G R Shellam
1Department of Microbiology, University of Western Australia, Nedlands.
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, Kq and/or Dq 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, Kj, Dk, Dj, 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 F1 progeny of H-2b X H-2k and H-2d X H-2k crosses, and was not compromised by the bm1, bm3, bm10, or bm14 mutations in the alpha 1 or alpha 2 regions of Kb or Db. 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-2k BMM and 46% of H-2k 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.
Insights
Murine cytomegalovirus (MCMV) infection susceptibility in macrophages and fibroblasts is determined by specific H-2 class I alleles. These H-2 K and D antigens are associated with the cellular receptor for MCMV.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Macrophages and fibroblasts are key cells in host defense against viral infections.
- Murine cytomegalovirus (MCMV) is a widely studied model virus for herpesvirus infections.
- The H-2 complex in mice encodes class I and class II major histocompatibility complex (MHC) molecules, crucial for immune responses.
Purpose of the Study:
- To investigate the role of H-2 class I alleles in determining susceptibility of different mouse cell types to MCMV infection.
- To identify specific H-2 haplotypes associated with resistance or sensitivity to MCMV.
- To explore the genetic basis of MCMV cellular tropism.
Main Methods:
- Infection of peritoneal macrophages (PM), bone marrow-derived macrophages (BMM), and lung fibroblasts (LF) from various inbred, recombinant, mutant, and hybrid mice with MCMV.
- Centrifugal enhancement used to increase infection efficiency.
- Assessment of infection levels via viral antigen expression and Fc receptor loss.
Main Results:
- Peritoneal macrophages from mice carrying specific H-2 alleles (Kd, Kb, Dd, Ks, Ds, Kq, Dq) showed high susceptibility (80%-100%) to MCMV.
- Cells with H-2 haplotypes Kk, Kj, Dk, Dj, or Db were resistant (<20% infection).
- Susceptibility was dominant in F1 hybrids and not affected by mutations in the alpha 1 or alpha 2 regions of Kb or Db, indicating the involvement of class I H-2 K and D antigens.
Conclusions:
- H-2 class I genotype, specifically K and D antigens, dictates susceptibility to MCMV infection in macrophages and lung fibroblasts.
- These findings suggest an association between H-2 K and D antigens and a cellular receptor for MCMV.
- The genetic background (non-H-2) and class II genotype did not influence MCMV infection proportions.