A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits Hepatitis C virus cell-cell transmission

Autor: Isabel Fofana, Christine Thumann, Fritz Grunert, Thomas F. Baumert, Fei Xiao, Marine Turek, Rajiv G. Tawar, John F. Thompson, Laetitia Zona, Mirjam B. Zeisel
Přispěvatelé: Baumert, Thomas F., Programme 'Chaires d'excellence': aide à l'accueil de chercheurs et d'enseignants chercheurs de haut niveau venant de l'étranger - Infection par le virus de l'hépatite C : Etude des interactions virus-cellule cible et des mécanismes impliqués dans la pathogénie de l'infection - - HCV HOST INTERACTION2005 - ANR-05-CEXC-0008 - CEXC - VALID, Molecular Analysis of Hepatitis C Virus Neutralization and Entry For the Development of Novel Antiviral Immunopreventive Strategies - HEPCENT - - EC:FP7:ERC2009-04-01 - 2014-03-31 - 233130 - VALID, Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Aldevron GmbH, his work was supported by Inserm, University of Strasbourg, the European Union (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Supe ́rieur- FEDER-Hepato-Regio-Net 2009 and 2012), the chair of excellence program of the Agence Nationale de la Recherche France (ANR-05-CEXC-008), ANRS (2009/183, 2011/132, 2012/239), Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir, ANR-10-LAB-28), the Direction Ge ́ne ́rale de l'Offre de Soins (A12027MS) and Aldevron (Pro Inno II (KA0690901UL8))., ANR-05-CEXC-0008,HCV HOST INTERACTION,Infection par le virus de l'hépatite C : Etude des interactions virus-cellule cible et des mécanismes impliqués dans la pathogénie de l'infection(2005), European Project: 233130,EC:FP7:ERC,ERC-2008-AdG,HEPCENT(2009)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Anatomy and Physiology
Gastroenterology and hepatology
Cancer Treatment
lcsh:Medicine
Hepacivirus
Drug resistance
medicine.disease_cause
Hepatitis
0302 clinical medicine
Viral Envelope Proteins
Immune Physiology
lcsh:Science
0303 health sciences
Multidisciplinary
biology
Antibodies
Monoclonal
virus diseases
Antivirals
Hepatitis C
Immunizations
3. Good health
Infectious hepatitis
Oncology
Monoclonal
Medicine
Infectious diseases
030211 gastroenterology & hepatology
Antibody
Research Article
medicine.drug_class
Hepatitis C virus
Immunology
Viral diseases
Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Monoclonal antibody
Microbiology
Antibodies
Tetraspanin 28
03 medical and health sciences
Antibody Therapy
Viral entry
Virology
medicine
Animals
Humans
Rats
Wistar
Biology
Liver diseases
030304 developmental biology
lcsh:R
Cell Membrane
Immunity
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Hepatitis C Antibodies
Virus Internalization
Antibodies
Neutralizing
digestive system diseases
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Rats
Immunization
biology.protein
lcsh:Q
Clinical Immunology
CD81
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e64221. ⟨10.1371/journal.pone.0064221⟩
PLoS ONE, Vol 8, Iss 5, p e64221 (2013)
PLoS ONE, 2013, 8 (5), pp.e64221. ⟨10.1371/journal.pone.0064221⟩
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0064221⟩
Popis: International audience; BACKGROUND AND AIMS: 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. CONCLUSION: 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.
Databáze: OpenAIRE
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