Jenssen Håvard, Sandvik Kjersti, Andersen Jeanette H, Hancock Robert E W, Gutteberg Tore J
Department of Medical Microbiology, University Hospital of North Norway, N-9038 Tromsø, Norway.
Antiviral Res. 2008 Sep;79(3):192-8. doi: 10.1016/j.antiviral.2008.03.004. Epub 2008 Apr 21.
The milk protein lactoferrin (Lf) has multiple functions, including immune stimulation and antiviral activity towards herpes simplex virus 1 and 2 (HSV-1 and HSV-2); antiviral activity has also been reported for the N-terminal pepsin-derived fragment lactoferricin (Lfcin). The anti-HSV mode of action of Lf and Lfcin is assumed to involve, in part, their interaction with the cell surface glycosaminoglycan heparan sulfate, thereby blocking of viral entry. In this study we investigated the ability of human and bovine Lf and Lfcin to inhibit viral cell-to-cell spread as well as the involvement of cell surface glycosaminoglycans during viral cell-to-cell spread. Lf and Lfcin from both human and bovine origin, inhibited cell-to-cell spread of both HSV-1 and HSV-2. Inhibition of cell-to-cell spread by bovine Lfcin involved cell surface chondroitin sulfate. Based on transmission electron microscopy studies, human Lfcin, like bovine Lfcin, was randomly distributed intracellularly, thus differences in their antiviral activity could not be explained by differences in their distribution. In contrast, the cellular localization of iron-saturated (holo)-Lf appeared to differ from that of apo-Lf, indicating that holo- and apo-Lf may exhibit different antiviral mechanisms.
乳蛋白乳铁蛋白（Lf）具有多种功能，包括免疫刺激以及对单纯疱疹病毒1型和2型（HSV-1和HSV-2）的抗病毒活性；据报道，N端胃蛋白酶衍生片段乳铁传递蛋白（Lfcin）也具有抗病毒活性。Lf和Lfcin的抗HSV作用模式被认为部分涉及它们与细胞表面糖胺聚糖硫酸乙酰肝素的相互作用，从而阻断病毒进入。在本研究中，我们研究了人和牛的Lf及Lfcin抑制病毒细胞间传播的能力，以及病毒细胞间传播过程中细胞表面糖胺聚糖的作用。人和牛来源的Lf和Lfcin均抑制了HSV-1和HSV-2的细胞间传播。牛Lfcin对细胞间传播的抑制涉及细胞表面硫酸软骨素。基于透射电子显微镜研究，人Lfcin与牛Lfcin一样，在细胞内随机分布，因此它们抗病毒活性的差异无法用其分布差异来解释。相反，铁饱和（全）-Lf的细胞定位似乎与脱铁-Lf不同，这表明全-Lf和脱铁-Lf可能表现出不同的抗病毒机制。
