MHC proteins and heparan sulphate proteoglycans regulate murine cytomegalovirus infection

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Abstract
Factors influencing MCMV infection mediated by MHC class I molecules were analysed further as previous studies showed that the effects of the MHC genotype on sensitivity to this virus are important in vivo. Here we show that H‐2d, H‐2b, H‐2r and H‐2v macrophages are highly sensitive to MCMV. Moreover, transfection of H‐2k L‐cells with Kb or Dd conferred sensitivity to MCMV. This was not affected by amino acid substitutions in Kbα1 or α2, although previous studies demonstrated that exchange of the αl domain of Dd with Ldα1 compromised sensitivity. Here replacement of Kbα3 with Ldα3 reduced susceptibility to low doses of MCMV. In addition, extracellular β2‐microglobulin (β2m) promoted infection of β2m‐negative R1E/TL8X.1 cells transfected with Db with or without a β2m gene. Hence MCMV infection can involve p2m and the al and β3 domains of MHC heavy chains. MCMV infection of L‐cells expressing Dd or Kb was also inhibited by heparin, but infection of the parental L‐cell line was not reproducibly affected. A role for heparan sulphate proteoglycan in MHC‐mediated MCMV infection was confirmed using cells pre‐treated with heparinase I or III, or propagated in chlorate to inhibit the sulphation of the glycosaminoglycan chains.