Cytomegaloviruses (CMV) express a range of immunomodulatory genes, many of which exhibit considerable genetic variability. A number of the most prominent immunomodulatory genes are those that target the major histocompatibility (MHC) class I antigen presentation pathway. Murine CMV (MCMV) encodes three genes; m04, m06 and m152, that interfere with MHC class I expression at the surface of infected cells. Presumably these genes are important in ensuring viral persistence in important organs of transmission such as the salivary gland. MHC class I molecules are also highly variable and we propose that the genetic variability of genes that target these molecules exists to enable survival of MCMV in outbred host populations.
The purpose of our study was to determine if the genetic variation seen in the three immunomodulatory genes alters the capacity of MCMV variants to down-modulate MHC I. The level of MHC I present on the surface of infected cells was measured by flow cytometry. We show here that MCMV strains differ markedly in their capacity to down-modulate host MHC I. Our data suggest that genetic variability of the m04 gene is associated with these differences. Strains of MCMV that express the same m04 genotype exhibit similar patterns of MHC I cell surface expression. We propose, therefore, that differences in MHC I cell surface expression between strains of MCMV is the result of differential reestablishment of MHC I molecules on the surface of infected cells, predominantly mediated by m04.