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 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.
School of Life Sciences, and Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK.
Mohamed R
MR
Hamed
Richard J P
RJ
Brown
Carsten
C
Zothner
Richard A
RA
Urbanowicz
Christopher P
CP
Mason
Anders
A
Krarup
C Patrick
CP
McClure
William L
WL
Irving
Jonathan K
JK
Ball
Mark
M
Harris
Timothy P
TP
Hickling
Alexander W
AW
Tarr
D037582:Complement Pathway, Mannose-Binding Lectin; D057809:HEK293 Cells; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology* / Q000635:transmission; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D011485:Protein Binding / Q000187:drug effects; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014774:Virulence; D053586:Virus Internalization / Q000187:drug effects; D000097604:Ficolins
D037102:Lectins; D051192:Receptors, Pattern Recognition; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D000097604:Ficolins; C087035:E1 protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus