MHC proteins and heparan sulphate proteoglycans regulate murine cytomegalovirus infection

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‐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^bα1 or α2, although previous studies demonstrated that exchange of the αl domain of D^d with L^dα1 compromised sensitivity. Here replacement of K^bα3 with L^dα3 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.