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 opsoniz...
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| Format: | Article |
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Karger
2014
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| Online Access: | https://eprints.nottingham.ac.uk/47402/ |
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| author | 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. Harrison, Mark Hickling, Timothy P. Tarr, Alexander W. |
| author_facet | 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. Harrison, Mark Hickling, Timothy P. Tarr, Alexander W. |
| author_sort | Hamed, Mohamed R. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:05:27Z |
| format | Article |
| id | nottingham-47402 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:05:27Z |
| publishDate | 2014 |
| publisher | Karger |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-474022020-05-04T16:47:53Z https://eprints.nottingham.ac.uk/47402/ 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. Harrison, Mark Hickling, Timothy P. Tarr, Alexander W. 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. Karger 2014-05-15 Article PeerReviewed 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., Harrison, Mark, 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 Hepatitis C virus; Ficolin virus entry; Neutralization; Glycosylation https://doi.org/10.1159/000362209 doi:10.1159/000362209 doi:10.1159/000362209 |
| spellingShingle | Hepatitis C virus; Ficolin virus entry; Neutralization; Glycosylation 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. Harrison, Mark Hickling, Timothy P. Tarr, Alexander W. Recombinant human L-ficolin directly neutralizes hepatitis C virus entry |
| title | Recombinant human L-ficolin directly neutralizes hepatitis C virus entry |
| title_full | Recombinant human L-ficolin directly neutralizes hepatitis C virus entry |
| title_fullStr | Recombinant human L-ficolin directly neutralizes hepatitis C virus entry |
| title_full_unstemmed | Recombinant human L-ficolin directly neutralizes hepatitis C virus entry |
| title_short | Recombinant human L-ficolin directly neutralizes hepatitis C virus entry |
| title_sort | recombinant human l-ficolin directly neutralizes hepatitis c virus entry |
| topic | Hepatitis C virus; Ficolin virus entry; Neutralization; Glycosylation |
| url | https://eprints.nottingham.ac.uk/47402/ https://eprints.nottingham.ac.uk/47402/ https://eprints.nottingham.ac.uk/47402/ |