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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.

Authors

Mohamed R. Hamed

Richard J.P. Brown

Carsten Zothner

Richard A. Urbanowicz

Christopher P. Mason

Anders Krarup

C. Patrick McClure

William L. Irving

Jonathan K. Ball

Mark Harris

Timothy P. Hickling

Alexander W. Tarr



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.

Journal Article Type Article
Publication Date 2014
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
APA6 Citation Hamed, M. R., Brown, R. J., Zothner, C., Urbanowicz, R. A., Mason, C. P., Krarup, A., …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
DOI https://doi.org/10.1159/000362209
Keywords Hepatitis C virus; Ficolin virus entry; Neutralization; Glycosylation
Publisher URL https://doi.org/10.1159/000362209
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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