Recombinant Human L-Ficolin Directly Neutralizes Hepatitis C Virus Entry

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.

Abstract

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.

Citation

Hamed, M. R., Brown, R. J., Zothner, C., Urbanowicz, R. A., Mason, C. P., Krarup, A., McClure, C. P., Irving, W. L., Ball, J. K., Harris, M., Hickling, T. P., & Tarr, A. W. (2014). Recombinant Human L-Ficolin Directly Neutralizes Hepatitis C Virus Entry. Journal of Innate Immunity, 6(5), 676-684. https://doi.org/10.1159/000362209

• Journal Article Type: Article
• Acceptance Date: Mar 16, 2014
• Online Publication Date: May 15, 2014
• Publication Date: 2014
• Deposit Date: Oct 20, 2017
• Publicly Available Date: Oct 20, 2017
• Journal: Journal of Innate Immunity
• Print ISSN: 1662-811X
• Electronic ISSN: 1662-8128
• Publisher: Karger Publishers
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 5
• Pages: 676-684
• DOI: https://doi.org/10.1159/000362209
• Keywords: Hepatitis C virus; Ficolin virus entry; Neutralization; Glycosylation
• Public URL: https://nottingham-repository.worktribe.com/output/728556
• Publisher URL: https://doi.org/10.1159/000362209
• Additional Information: This is the peer-reviewed but unedited manuscript version of the following article: Hamed M, R, Brown R, J, P, Zothner C, Urbanowicz R, A, Mason C, P, Krarup A, McClure C, P, Irving W, L, Ball J, K, Harris M, Hickling T, P, Tarr A, W, Recombinant Human L-Ficolin Directly Neutralizes Hepatitis C Virus Entry. J Innate Immun 2014;6:676-684(DOI: 10.1159/000362209)]. The final, published version is available at http://www.karger.com/10.1159/000362209
• Contract Date: Oct 20, 2017