MHC proteins and heparan sulphate proteoglycans regulate murine cytomegalovirus infection

Summary 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‐2 d , H‐2 b , H‐2 r and H‐2 v macrophages are highly sensitive to MCMV. Moreover, transfection of H‐2 k L‐cells with Kb or D d conferred sensitivity to MCMV. This was not affected by amino acid substitutions in K b α1 or α2, although previous studies demonstrated that exchange of the αl domain of D d with L d α1 compromised sensitivity. Here replacement of K b α3 with L d α3 reduced susceptibility to low doses of MCMV. In addition, extracellular β2‐microglobulin (β2m) promoted infection of β2m‐negative R1E/TL8X.1 cells transfected with D b 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 D d or K b 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.