Enhancement of Ebola Virus Infection via Ficolin-1 Interaction with the Mucin Domain of GP Glycoprotein

J Virol. 2016 May 12;90(11):5256-5269. doi: 10.1128/JVI.00232-16. Print 2016 Jun 1.


Ebola virus infection requires the surface viral glycoprotein to initiate entry into the target cells. The trimeric glycoprotein is a highly glycosylated viral protein which has been shown to interact with host C-type lectin receptors and the soluble complement recognition protein mannose-binding lectin, thereby enhancing viral infection. Similarly to mannose-binding lectin, ficolins are soluble effectors of the innate immune system that recognize particular glycans at the pathogen surface. In this study, we demonstrate that ficolin-1 interacts with the Zaire Ebola virus (EBOV) glycoprotein, and we characterized this interaction by surface plasmon resonance spectroscopy. Ficolin-1 was shown to bind to the viral glycoprotein with a high affinity. This interaction was mediated by the fibrinogen-like recognition domain of ficolin-1 and the mucin-like domain of the viral glycoprotein. Using a ficolin-1 control mutant devoid of sialic acid-binding capacity, we identified sialylated moieties of the mucin domain to be potential ligands on the glycoprotein. In cell culture, using both pseudotyped viruses and EBOV, ficolin-1 was shown to enhance EBOV infection independently of the serum complement. We also observed that ficolin-1 enhanced EBOV infection on human monocyte-derived macrophages, described to be major viral target cells,. Competition experiments suggested that although ficolin-1 and mannose-binding lectin recognized different carbohydrate moieties on the EBOV glycoprotein, the observed enhancement of the infection likely depended on a common cellular receptor/partner. In conclusion, ficolin-1 could provide an alternative receptor-mediated mechanism for enhancing EBOV infection, thereby contributing to viral subversion of the host innate immune system.

Importance: A specific interaction involving ficolin-1 (M-ficolin), a soluble effector of the innate immune response, and the glycoprotein (GP) of EBOV was identified. Ficolin-1 enhanced virus infection instead of tipping the balance toward its elimination. An interaction between the fibrinogen-like recognition domain of ficolin-1 and the mucin-like domain of Ebola virus GP occurred. In this model, the enhancement of infection was shown to be independent of the serum complement. The facilitation of EBOV entry into target host cells by the interaction with ficolin-1 and other host lectins shunts virus elimination, which likely facilitates the survival of the virus in infected host cells and contributes to the virus strategy to subvert the innate immune response.

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Complement System Proteins / metabolism
  • Ebolavirus / chemistry
  • Ebolavirus / genetics
  • Ebolavirus / metabolism*
  • HEK293 Cells
  • Humans
  • Lectins / metabolism*
  • Macrophages / virology
  • Mannose-Binding Lectin / metabolism
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism*
  • Mucins / metabolism*
  • Mutation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Vero Cells
  • Viral Envelope Proteins / metabolism
  • Virus Internalization


  • Lectins
  • Mannose-Binding Lectin
  • Membrane Glycoproteins
  • Mucins
  • Viral Envelope Proteins
  • ficolin
  • Complement System Proteins

Grant support

We acknowledge the support of the Direction Générale pour l'Armement (DGA), the Service de Santé des Armées (PDH-2-NRBC-4-B2-408), and ARAMI. This work used the platforms of the Grenoble Instruct Centre (ISBG; UMS 3518 CNRS-CEA-UGA-EMBL) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble Partnership for Structural Biology (PSB).