Marchetti M, Longhi C, Conte M P, Pisani S, Valenti P, Seganti L
Microbiology Institute, University of Rome, La Sapienza, Italy.
Antiviral Res. 1996 Mar;29(2-3):221-31. doi: 10.1016/0166-3542(95)00840-3.
This paper describes the ability of human and bovine lactoferrins (HLf; BLf), iron-binding proteins belonging to the non-immune defense system, to interfere with herpes simplex virus type 1 (HSV-1) infection. Since lactoferrins are known to bind to heparan sulphate proteoglycans and to low density lipoprotein receptor, which in turn act as binding sites for the initial interaction of HSV-1 with host cells, we tested the effect of these proteins on HSV-1 multiplication in Vero cells. Both HLf and BLf are found to be potent inhibitors of HSV-1 infection, the concentrations required to inhibit the vital cytopathic effect in Vero cells by 50% being 1.41 microM and 0.12 microM, respectively. HLf and BLf exerted their activity through the inhibition of adsorption of virions to the cells independently of their iron withholding property showing similar activity in the apo- and iron-saturated form. The binding of [35S]methionine-labelled HSV-1 particles to Vero cells was strongly inhibited when BLf was added during the attachment step. BLf interacts with both Vero cell surfaces and HSV-1 particles, suggesting that the hindrance of cellular receptors and/or of viral attachment proteins may be involved in its antiviral mechanism.
本文描述了人乳铁蛋白和牛乳铁蛋白(HLf;BLf)这两种属于非免疫防御系统的铁结合蛋白干扰单纯疱疹病毒1型(HSV-1)感染的能力。由于已知乳铁蛋白可与硫酸乙酰肝素蛋白聚糖和低密度脂蛋白受体结合,而这两者又充当HSV-1与宿主细胞初始相互作用的结合位点,因此我们测试了这些蛋白对Vero细胞中HSV-1增殖的影响。结果发现HLf和BLf都是HSV-1感染的有效抑制剂,在Vero细胞中抑制50%的细胞病变效应所需的浓度分别为1.41微摩尔和0.12微摩尔。HLf和BLf通过抑制病毒粒子吸附到细胞上发挥其活性,与它们的铁扣留特性无关,在脱辅基形式和铁饱和形式下表现出相似的活性。在吸附步骤中加入BLf时,[35S]甲硫氨酸标记的HSV-1颗粒与Vero细胞的结合受到强烈抑制。BLf与Vero细胞表面和HSV-1颗粒都相互作用,这表明细胞受体和/或病毒附着蛋白的阻碍可能参与了其抗病毒机制。