title: A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits Hepatitis C virus cell-cell transmission.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is a challenge to prevent and treat because of the rapid development of drug resistance and escape. Viral entry is required for initiation, spread, and maintenance of infection, making it an attractive target for antiviral strategies.
  
  
  METHODS
  Using genetic immunization, we produced four monoclonal antibodies (mAbs) against the HCV host entry factor CD81. The effects of antibodies on inhibition of HCV infection and dissemination were analyzed in HCV permissive human liver cell lines.
  
  
  RESULTS
  The anti-CD81 mAbs efficiently inhibited infection by HCV of different genotypes as well as a HCV escape variant selected during liver transplantation and re-infecting the liver graft. Kinetic studies indicated that anti-CD81 mAbs target a post-binding step during HCV entry. In addition to inhibiting cell-free HCV infection, one antibody was also able to block neutralizing antibody-resistant HCV cell-cell transmission and viral dissemination without displaying any detectable toxicity.
  
  
  CONCLUSIONS
  A novel anti-CD81 mAb generated by genetic immunization efficiently blocks HCV spread and dissemination. This antibody will be useful to further unravel the role of virus-host interactions during HCV entry and cell-cell transmission. Furthermore, this antibody may be of interest for the development of antivirals for prevention and treatment of HCV infection.
authors.affiliation: Inserm, U1110, Institute of Virology, Strasbourg, France.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fofana
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Christine
authors.initials: C
authors.lastname: Thumann
authors.forename: Marine
authors.initials: M
authors.lastname: Turek
authors.forename: Laetitia
authors.initials: L
authors.lastname: Zona
authors.forename: Rajiv G
authors.initials: RG
authors.lastname: Tawar
authors.forename: Fritz
authors.initials: F
authors.lastname: Grunert
authors.forename: John
authors.initials: J
authors.lastname: Thompson
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051381:Rats; D017208:Rats, Wistar; D060225:Tetraspanin 28 / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D053586:Virus Internalization
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D018937:Hepatitis C Antibodies; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins