Recombinant human L-ficolin directly neutralizes hepatitis C virus entry

Hamed, Mohamed R. and Brown, Richard J.P. and Zothner, Carsten and Urbanowicz, Richard A. and Mason, Christopher P. and Krarup, Anders and McClure, C. Patrick and Irving, William L. and Ball, Jonathan K. and Harrison, Mark and Hickling, Timothy P. and Tarr, Alexander W. (2014) Recombinant human L-ficolin directly neutralizes hepatitis C virus entry. Journal of Innate Immunity, 6 (5). pp. 676-684. ISSN 1662-8128

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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.

Item Type: Article
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
Keywords: Hepatitis C virus; Ficolin virus entry; Neutralization; Glycosylation
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1159/000362209
Depositing User: Eprints, Support
Date Deposited: 20 Oct 2017 07:55
Last Modified: 20 Oct 2017 11:35
URI: http://eprints.nottingham.ac.uk/id/eprint/47402

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