Recombinant Human L-ficolin Directly Neutralizes Hepatitis C Virus Entry

Overview

Journal J Innate Immun

Publisher Karger

Specialty Allergy & Immunology

Date 2014 May 24

PMID 24854201

Citations 15

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

Affiliations

Soon will be listed here.

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.

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