Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Abstract

L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus (HCV), were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.1. Investigation of the mechanisms of the L-ficolin action on HCV demonstrated that L-ficolin protein could recognize and bind to envelope glycoproteins E1 and E2 of HCV, activating the lectin complement pathway-mediated cytolytic activity in HCV-infected hepatocyte. This interaction between L-ficolin and HCV E1 and E2 glycoproteins was attributed to the N-glycans of E1 and E2. These findings provide new insights into the biological functions of L-ficolin in clinically important hepatic viral diseases.

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Glossary

HCV

hepatitis C virus

PBMC

peripheral blood mononuclear cells

DC

dendritic cells

BCECF

bis-carboxyethyl-carboxyfluorescein

MBL

mannan-binding lectin

PAMP

pathogen-associated molecules pattern

GAPDH

glyceraldehydes-3-phosphate dehydrogenase