title: Acute hepatitis C virus infection induces anti-host cell receptor antibodies with virus-neutralizing properties.
abstract: Hepatitis C virus (HCV) causes persistent infection in the majority of infected individuals. The mechanisms of persistence and clearance are only partially understood. Antibodies (Abs) against host cell entry receptors have been shown to inhibit HCV infection in cell culture and animal models. In this study, we aimed to investigate whether anti-receptor Abs are induced during infection in humans in vivo and whether their presence is associated with outcome of infection. We established an enzyme-linked immunosorbant assay using a recombinant CD81-claudin-1 (CLDN1) fusion protein to detect and quantify Abs directed against extracellular epitopes of the HCV CD81-CLDN1 coreceptor complex. The presence of anti-receptor Abs was studied in serum of patients from a well-defined cohort of a single-source HCV outbreak of pregnant women and several control groups, including uninfected pregnant women, patients with chronic hepatitis B and D virus (HBV/HDV) infection, and healthy individuals. Virus-neutralizing activity of Abs was determined using recombinant cell culture-derived HCV (HCVcc). Our results demonstrate that HCV-infected patients have statistically significantly higher anti-CD81/CLDN1 Ab titers during the early phase of infection than controls. The titers were significantly higher in resolvers compared to persisters. Functional studies using immunoadsorption and HCV cell culture models demonstrate that HCV-neutralizing anti-receptor Abs are induced in the early phase of HCV infection, but not in control groups.
  
  
  CONCLUSIONS
  The virus-neutralizing properties of these Abs suggest a role for control of viral infection in conjunction with antiviral responses. Characterization of these anti-receptor Abs opens new avenues to prevent and treat HCV infection.
authors.affiliation: Inserm, U1110, Institut des Maladies Virales et Hépatiques, Strasbourg, France.|University of Strasbourg, Strasbourg, France.
authors.forename: Rajiv G
authors.initials: RG
authors.lastname: Tawar
authors.affiliation: Inserm, U1110, Institut des Maladies Virales et Hépatiques, Strasbourg, France.|University of Strasbourg, Strasbourg, France.
authors.forename: Che C
authors.initials: CC
authors.lastname: Colpitts
authors.affiliation: Institute for Virology, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Timm
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.affiliation: Institute of Virology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.affiliation: Institute of Medical Virology, Helmut-Ruska-Haus, Charité University Medicine, Berlin, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Meisel
authors.affiliation: Pôle de Santé Publique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Inserm, U1110, Institut des Maladies Virales et Hépatiques, Strasbourg, France.|University of Strasbourg, Strasbourg, France.|Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Habersetzer
authors.affiliation: CIRI-International Center for Infectiology Research, Lyon, France; Inserm, U1111, Lyon France; Ecole Normale Supérieure; CNRS UMR 5308, Lyon, France; LabEx Ecofect, University of Lyon, Lyon, France.
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.affiliation: Department of Internal Medicine, Neurology and Dermatology, Gastroenterology and Rheumatology Clinic, Section of Hepatology, University of Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Inserm, U1110, Institut des Maladies Virales et Hépatiques, Strasbourg, France.|University of Strasbourg, Strasbourg, France.
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.affiliation: Inserm, U1110, Institut des Maladies Virales et Hépatiques, Strasbourg, France.|University of Strasbourg, Strasbourg, France.|Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D062445:Claudin-1 / Q000378:metabolism / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D009010:Monte Carlo Method; D011247:Pregnancy; D012372:ROC Curve; D011991:Receptors, Virus / Q000187:drug effects / Q000276:immunology; D012494:Sampling Studies; D060225:Tetraspanin 28 / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects*; D055815:Young Adult
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D011991:Receptors, Virus; D060225:Tetraspanin 28