Work

Binding of Free and Immune Complex‐Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System

Year: 2018

Type: article

Abstract: Erythrocytes bind circulating immune complexes (ICs) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC‐related disorders. In this study, we investigated the kinetics and mechanism of HCV and HCV‐IC binding to and dissociation from erythrocytes. Cell culture‐produced HCV was mixed with erythrocytes from healthy blood donors, and erythrocyte‐associated virus particles were quantified. Purified complement proteins, complement‐depleted serum, and complement receptor antibodies were used to investigate complement‐mediated HCV‐erythrocyte binding. Purified HCV‐specific immunoglobulin G (IgG) from a chronic HCV‐infected patient was used to study complement‐mediated HCV‐IC/erythrocyte binding. Binding of HCV to erythrocytes increased 200‐ to 1,000‐fold after adding complement active human serum in the absence of antibody. Opsonization of free HCV occurred within 10 minutes, and peak binding to erythrocytes was observed at 20‐30 minutes. Complement protein C1 was required for binding, whereas C2, C3, and C4 significantly enhanced binding. Complement receptor 1 (CR1, CD35) antibodies blocked the binding of HCV to erythrocytes isolated from chronically infected HCV patients and healthy blood donors. HCV‐ICs significantly enhanced complement‐mediated binding to erythrocytes compared to unbound HCV. Dissociation of complement‐opsonized HCV from erythrocytes depended on the presence of Factor I. HCV released by Factor I bound preferentially to CD19+ B cells compared to other leukocytes. Conclusion: These results demonstrate that complement mediates the binding of free and IC‐associated HCV to CR1 on erythrocytes and provide a mechanistic rationale for investigating the differential phenotypic expression of HCV‐IC–related disease.

Source: Hepatology

DOI: 10.1002/hep.30087

Authors: Kazi Abdus Salam, Richard Y. Wang, Teresa Grandinetti, Valeria De Giorgi, Harvey J. Alter, Robert D. Allison

Institutions: National Institutes of Health, National Institutes of Health Clinical Center, University of Rajshahi

Language: English

Topic: Complement system in diseases

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institutes of Health