MHC proteins and heparan sulphate proteoglycans regulate murine cytomegalovirus infection.
Factors influencing MCMV infection mediated by MHC class 1 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 Kb alpha 1 or alpha 2, although previous studies demonstrated that exchange of the alpha 1 domain of Dd with Ld alpha 1 compromised sensitivity. Here replacement of Kb alpha 3 with Ld alpha 3 reduced susceptibility to low doses of MCMV. In addition, extracellular beta 2-microglobulin (beta 2m) promoted infection of beta 2m-negative RIE/TL8X.1 cells transfected with Db with or without a beta 2m gene. Hence MCMV infection can involve beta 2m and the alpha 1 and alpha 3 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.
D000818:Animals; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics; D005805:Genes, MHC Class I / Q000276:immunology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006183:H-2 Antigens / Q000235:genetics / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007739:L Cells; D008563:Membrane Lipids / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000276:immunology; D011107:Polylysine / Q000494:pharmacology
D006025:Glycosaminoglycans; D006183:H-2 Antigens; D006493:Heparin; D006497:Heparan Sulfate; D008563:Membrane Lipids; D011107:Polylysine