Supplementary Material for: Recombinant Human L-Ficolin Directly Neutralizes Hepatitis C Virus Entry

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（L-ficolin）是一种由肝脏表达的可溶性模式识别分子，参与机体针对微生物的先天免疫防御。已有充分研究表明，L-纤维胶凝蛋白与特定病原体相关分子模式结合后，可激活凝集素补体通路，进而介导病原体的调理作用与裂解。本研究证实，除上述间接免疫效应外，L-纤维胶凝蛋白还可对丙型肝炎病毒（HCV）的入侵过程产生直接中和活性。研究观察到，重组L-纤维胶凝蛋白可与HCV糖蛋白E1和E2发生特异性、剂量依赖性结合，且该相互作用可被可溶性L-纤维胶凝蛋白配体所阻断。L-纤维胶凝蛋白与E1、E2的结合可强效抑制携带上述糖蛋白的逆转录病毒假病毒的入侵能力；此外，L-纤维胶凝蛋白还可通过钙依赖途径抑制细胞培养型HCV的入侵。研究发现，HCV感染者的血清中存在具有中和活性的循环L-纤维胶凝蛋白。本研究首次报道了纤维胶凝蛋白家族成员可直接中和HCV的入侵过程，同时揭示了L-纤维胶凝蛋白作为病毒入侵抑制剂的全新功能。