Specific interaction of hepatitis C virus glycoproteins with mannan binding lectin inhibits virus entry.
10.1007/s13238-010-0088-9
- Author:
Kristelle S BROWN
1
;
Michael J KEOGH
;
Ania M OWSIANKA
;
Richard ADAIR
;
Arvind H PATEL
;
James N ARNOLD
;
Jonathan K BALL
;
Robert B SIM
;
Alexander W TARR
;
Timothy P HICKLING
Author Information
1. Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
- Publication Type:Journal Article
- MeSH:
Binding, Competitive;
Glycosylation;
Hepacivirus;
genetics;
pathogenicity;
physiology;
Humans;
Mannose-Binding Lectin;
metabolism;
Mannose-Binding Protein-Associated Serine Proteases;
metabolism;
Monosaccharides;
metabolism;
Protein Binding;
Protein Multimerization;
Tumor Cells, Cultured;
Viral Envelope Proteins;
metabolism;
Virion;
pathogenicity;
physiology;
Virus Internalization
- From:
Protein & Cell
2010;1(7):664-674
- CountryChina
- Language:English
-
Abstract:
Mannan-binding lectin (MBL) is a soluble innate immune protein that binds to glycosylated targets. MBL acts as an opsonin and activates complement, contributing to the destruction and clearance of infecting microorganisms. Hepatitis C virus (HCV) encodes two envelope glycoproteins E1 and E2, expressed as non-covalent E1/E2 heterodimers in the viral envelope. E1 and E2 are potential ligands for MBL. Here we describe an analysis of the interaction between HCV and MBL using recombinant soluble E2 ectodomain fragment, the full-length E1/E2 heterodimer, expressed in vitro, and assess the effect of this interaction on virus entry. A binding assay using antibody capture of full length E1/E2 heterodimers was used to demonstrate calcium dependent, saturating binding of MBL to HCV glycoproteins. Competition with various saccharides further confirmed that the interaction was via the lectin domain of MBL. MBL binds to E1/E2 representing a broad range of virus genotypes. MBL was shown to neutralize the entry into Huh-7 cells of HCV pseudoparticles (HCVpp) bearing E1/E2 from a wide range of genotypes. HCVpp were neutralized to varying degrees. MBL was also shown to neutralize an authentic cell culture infectious virus, strain JFH-1 (HCVcc). Furthermore, binding of MBL to E1/E2 was able to activate the complement system via MBL-associated serine protease 2. In conclusion, MBL interacts directly with HCV glycoproteins, which are present on the surface of the virion, resulting in neutralization of HCV particles.
