Price P, Allcock R J, Coombe D R, Shellam G R, McCluskey J
Department of Microbiology, University of Western Australia, Nedlands, Australia.
Immunol Cell Biol. 1995 Aug;73(4):308-15. doi: 10.1038/icb.1995.47.
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.
由于先前的研究表明MHC基因型对该病毒敏感性的影响在体内很重要，因此对影响MHC I类分子介导的巨细胞病毒（MCMV）感染的因素进行了进一步分析。在此我们表明，H-2d、H-2b、H-2r和H-2v巨噬细胞对MCMV高度敏感。此外，用Kb或Dd转染H-2k L细胞可使其对MCMV敏感。这不受Kb α1或α2中氨基酸取代的影响，尽管先前的研究表明用Ld α1替换Dd 的α1结构域会损害敏感性。在此，用Ld α3替换Kb α3可降低对低剂量MCMV的易感性。此外，细胞外β2微球蛋白（β2m）促进了用Db转染的有或没有β2m基因的β2m阴性RIE/TL8X.1细胞的感染。因此，MCMV感染可能涉及β2m以及MHC重链的α1和α3结构域。表达Dd或Kb的L细胞的MCMV感染也受到肝素的抑制，但亲本L细胞系的感染未受到可重复的影响。使用用肝素酶I或III预处理或在氯酸盐中培养以抑制糖胺聚糖链硫酸化的细胞，证实了硫酸乙酰肝素蛋白聚糖在MHC介导的MCMV感染中的作用。
