Hamed Mohamed R, Brown Richard J P, Zothner Carsten, Urbanowicz Richard A, Mason Christopher P, Krarup Anders, McClure C Patrick, Irving William L, Ball Jonathan K, Harris Mark, Hickling Timothy P, Tarr Alexander W
School of Life Sciences, and Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK.
J Innate Immun. 2014;6(5):676-84. doi: 10.1159/000362209. Epub 2014 May 15.
L-ficolin is a soluble pattern recognition molecule expressed by the liver that contributes to innate immune defense against microorganisms. It is well described that binding of L-ficolin to specific pathogen-associated molecular patterns activates the lectin complement pathway, resulting in opsonization and lysis of pathogens. In this study, we demonstrated that in addition to this indirect effect, L-ficolin has a direct neutralizing effect against hepatitis C virus (HCV) entry. Specific, dose-dependent binding of recombinant L-ficolin to HCV glycoproteins E1 and E2 was observed. This interaction was inhibited by soluble L-ficolin ligands. Interaction of L-ficolin with E1 and E2 potently inhibited entry of retroviral pseudoparticles bearing these glycoproteins. L-ficolin also inhibited entry of cell-cultured HCV in a calcium-dependent manner. Neutralizing concentrations of L-ficolin were found to be circulating in the serum of HCV-infected individuals. This is the first description of direct neutralization of HCV entry by a ficolin and highlights a novel role for L-ficolin as a virus entry inhibitor.
L-纤维胶凝蛋白是一种由肝脏表达的可溶性模式识别分子，有助于对微生物的天然免疫防御。众所周知，L-纤维胶凝蛋白与特定病原体相关分子模式的结合会激活凝集素补体途径，导致病原体的调理作用和裂解。在本研究中，我们证明，除了这种间接作用外，L-纤维胶凝蛋白对丙型肝炎病毒（HCV）进入具有直接中和作用。观察到重组L-纤维胶凝蛋白与HCV糖蛋白E1和E2有特异性、剂量依赖性结合。这种相互作用被可溶性L-纤维胶凝蛋白配体抑制。L-纤维胶凝蛋白与E1和E2的相互作用有效抑制了携带这些糖蛋白的逆转录病毒假颗粒的进入。L-纤维胶凝蛋白还以钙依赖的方式抑制细胞培养的HCV的进入。发现L-纤维胶凝蛋白的中和浓度在HCV感染个体的血清中循环。这是首次描述纤维胶凝蛋白对HCV进入的直接中和作用，并突出了L-纤维胶凝蛋白作为病毒进入抑制剂的新作用。
