Besançon F, Ankel H
Tex Rep Biol Med. 1977;35:282-92.
Specific cell membrane receptors for interferon have been postulated based on a variety of different observations, such as the following: trypsin treatment of monkey-mouse hybrid cells preferentially destroys sensitivity to primate interferon (9); syngeneic mice immunized with human-mouse hybrid cells develop surface-directed antibodies, which only block antiviral action of human interferon (24); interferon covalently bound to Sepharose beads retains its antiviral activity despite the fact that diameters of the beads are several times those of the cells (1,10,19); cells challenged with polyl:C to produce interferon do not develop resistance to viral infection in the presence of interferon antiserum (30). Interferon has a strong and specific affinity for the carbohydrate side chain of cell membrane gangliosides. Preincubation of Sepharose-bound interferon with gangliosides inhibits antiviral activity in the following order of potency: GM2 greater than or equal to GTl greater than GMl greater than or equal to GDla (3). Derivatives of GM2 lacking either terminal N-acetyl-galactosamine or terminal N-acetyl-neuraminic acid are not (or very little) inhibitory; in addition, binding to gangliosides is reversed by N-acetyl-neuraminyl-lactose, the trisaccharide common to all gangliosides. These data clearly demonstrate interferon's specificity for the carbohydrate moiety of the ganglioside molecule (6). Phaeseolus vulgaris lectin, which blocks antiviral action of interferon (4), also prevents binding of interferon to ganglioside-Sepharose affinity columns (2). Many substances of known affinity for gangliosides likewise inhibit action of interferon. These include cholera (15) and tetanus toxins (2), thyrotropin (5,23) and human chorionic gonadotropin (5). Although a more general effect on the state of the membrane or on cellular metabolism by these substances cannot be ruled out, competition for interferon binding sites appears to be the most plausible explanation. Increased sensitivity of certain transformed cells to interferon upon uptake of exogenous gangliosides not only supports the concept that these glycolipids are involved in binding of interferon to the membrane, but furthermore points to the importance of interferon-ganglioside interaction for triggering of the antiviral response (29).
基于各种不同的观察结果，人们推测存在干扰素的特异性细胞膜受体，如下所示：用胰蛋白酶处理猴 - 鼠杂交细胞会优先破坏对灵长类干扰素的敏感性（9）；用人 - 鼠杂交细胞免疫的同基因小鼠产生表面定向抗体，该抗体仅阻断人干扰素的抗病毒作用（24）；与琼脂糖珠共价结合的干扰素保留其抗病毒活性，尽管珠子的直径是细胞直径的几倍（1,10,19）；用聚肌胞苷酸刺激产生干扰素的细胞在存在干扰素抗血清的情况下不会对病毒感染产生抗性（30）。干扰素对细胞膜神经节苷脂的碳水化合物侧链具有强烈且特异性的亲和力。用神经节苷脂对结合琼脂糖的干扰素进行预孵育会按以下效力顺序抑制抗病毒活性：GM2大于或等于GT1大于GM1大于或等于GD1a（3）。缺乏末端N - 乙酰半乳糖胺或末端N - 乙酰神经氨酸的GM2衍生物衍生物衍生物没有（或几乎没有）抑制作用；此外，与神经节苷脂的结合可被N - 乙酰神经氨酰乳糖逆转，N - 乙酰神经氨酰乳糖是所有神经节苷脂共有的三糖。这些数据清楚地证明了干扰素对神经节苷脂分子碳水化合物部分的特异性（6）。菜豆凝集素可阻断干扰素的抗病毒作用（4），它也会阻止干扰素与神经节苷脂 - 琼脂糖亲和柱的结合（2）。许多已知对神经节苷脂有亲和力的物质同样会抑制干扰素的作用。这些物质包括霍乱毒素（15）和破伤风毒素（2）、促甲状腺激素（5,23）和人绒毛膜促性腺激素（5）。尽管不能排除这些物质对膜状态或细胞代谢有更普遍的影响，但对干扰素结合位点的竞争似乎是最合理的解释。某些转化细胞在摄取外源性神经节苷脂后对干扰素的敏感性增加，这不仅支持了这些糖脂参与干扰素与膜结合这一概念，而且还指出了干扰素 - 神经节苷脂相互作用对于触发抗病毒反应的重要性（29）。
