The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination

Autor: Marine Turek, Thomas F. Baumert, John F. Thompson, Viet Loan Dao Thi, Dorothea Bankwitz, Mirjam B. Zeisel, François-Loïc Cosset, Fei Xiao, Isabel Fofana, Johan Neyts, Marlène Dreux, Philippe Bachellier, Maryse Guerin, Fritz Grunert, Leen Delang, Thomas Pietschmann, Muhammad N. Zahid
Přispěvatelé: Baumert, Thomas F., 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, Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Dyslipidémies, inflammation et athérosclérose dans les maladies métaboliques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Hôpital de Hautepierre [Strasbourg], Aldevron GmbH, Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Division of Experimental Virology, Centre for Experimental and Clinical Infection Research (TWINCORE), Helmholtz Centre for Infection Research (HZI)-Medizinische Hochschule Hannover (MHH)-Helmholtz Centre for Infection Research (HZI)-Medizinische Hochschule Hannover (MHH), European Union (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2009), Laboratoire d'Excellence HEPSYS (Investissement d'Avenir, ANR-10-LAB-28), ANR-05-CEXC-008, ANRS (2008/354, 2009/183, 2011/132), Pro Inno II (KA0690901UL8), Région Alsace, Inserm, University of Strasbourg, and Aldevron Freiburg. The group in Leuven was funded by a grant from the Fund for Scientific Research (FWO) (G.0728.09N) and KULeuven GOA 10/014. M. N. Z. was supported by HEC fellowship., European Project: 233130,EC:FP7:ERC,ERC-2008-AdG,HEPCENT(2009), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre for Experimental and Clinical Infection Research [Hanover] (TWINCORE), Nouvel Hôpital Civil de Strasbourg, INSERM, U748, Strasbourg, France.
Jazyk: angličtina
Rok vydání: 2013
Předmět:
CD36 Antigens
[SDV]Life Sciences [q-bio]
Hepacivirus
Antigens
CD36
virus entry
medicine.disease_cause
MESH: Lipoproteins
HDL
MESH: Antibodies
Monoclonal
Mice
0302 clinical medicine
MESH: Animals
MESH: Hepacivirus
Receptor
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
0303 health sciences
biology
Hepatitis C virus
Antibodies
Monoclonal
scavenger receptor BI
Hepatitis C
antiviral
3. Good health
030211 gastroenterology & hepatology
Antibody
MESH: Cholesterol
HDL
Lipoproteins
HDL
MESH: Rats
medicine.drug_class
Monoclonal antibody
viral dissemination
Cell Line
03 medical and health sciences
Viral entry
medicine
Animals
Humans
Scavenger receptor
MESH: Receptors
Lipoprotein
MESH: Mice
030304 developmental biology
Receptors
Lipoprotein
MESH: Hepatitis C
MESH: Humans
Hepatology
MESH: Antigens
CD36
Cholesterol
HDL
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Virology
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Rats
MESH: Cell Line
chemistry
Cell culture
biology.protein
Glycoprotein
Zdroj: Hepatology
Hepatology, 2013, 57 (2), pp.492-504. ⟨10.1002/hep.26097⟩
Hepatology, Wiley-Blackwell, 2013, 57 (2), pp.492-504. ⟨10.1002/hep.26097⟩
ISSN: 0270-9139
1527-3350
DOI: 10.1002/hep.26097⟩
Popis: International audience; UNLABELLED: Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor highly expressed in the liver and modulating HDL metabolism. Hepatitis C virus (HCV) is able to directly interact with SR-BI and requires this receptor to efficiently enter into hepatocytes to establish productive infection. A complex interplay between lipoproteins, SR-BI and HCV envelope glycoproteins has been reported to take place during this process. SR-BI has been demonstrated to act during binding and postbinding steps of HCV entry. Although the SR-BI determinants involved in HCV binding have been partially characterized, the postbinding function of SR-BI remains largely unknown. To uncover the mechanistic role of SR-BI in viral initiation and dissemination, we generated a novel class of anti-SR-BI monoclonal antibodies that interfere with postbinding steps during the HCV entry process without interfering with HCV particle binding to the target cell surface. Using the novel class of antibodies and cell lines expressing murine and human SR-BI, we demonstrate that the postbinding function of SR-BI is of key impact for both initiation of HCV infection and viral dissemination. Interestingly, this postbinding function of SR-BI appears to be unrelated to HDL interaction but to be directly linked to its lipid transfer function. CONCLUSION: Taken together, our results uncover a crucial role of the SR-BI postbinding function for initiation and maintenance of viral HCV infection that does not require receptor-E2/HDL interactions. The dissection of the molecular mechanisms of SR-BI-mediated HCV entry opens a novel perspective for the design of entry inhibitors interfering specifically with the proviral function of SR-BI.
Databáze: OpenAIRE
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