title: The expression of the hepatocyte SLAMF3 (CD229) receptor enhances the hepatitis C virus infection.
abstract: Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. We recently characterized for the first time the expression of Signaling Lymphocyte Activating Molecule 3 (SLAMF3) in human hepatocytes and here, we report that SLAMF3 interacts with the HCV viral protein E2 and is implicated in HCV entry process. We found a strong correlation between SLAMF3 expression level and hepatocyte susceptibility to HCV infection. The use of specific siRNAs to down-modulate SLAMF3 expression and SLAMF3-blocking antibodies both decreased the hepatocytes susceptibility to HCV infection. Moreover, SLAMF3 over-expression significantly increased susceptibility to HCV infection. Interestingly, experiments with peptides derived from each SLAMF3 domain showed that the first N-terminal extracellular domain is essential for interaction with HCV particles. Finally, we showed that recombinant HCV envelop protein E2 can bind SLAMF3 and that anti-SLAMF3 antibodies inhibited specifically this interaction. Overall, our results revealed that SLAMF3 plays a role during HCV entry, likely by enhancing entry of viral particle within hepatocytes.
authors.affiliation: EA 4666, UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France; INSERM U1053, Laboratoire de Physiologie du Cancer du Foie, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Cartier
authors.affiliation: EA 4666, UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Marcq
authors.affiliation: UMR CNRS 5557 Ecologie Microbienne, Université Lyon 1, Villeurbanne, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Douam
authors.affiliation: EA 4666, UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France; Laboratoire de Thérapie Cellulaire, CHU Amiens Sud, Amiens, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Ossart
authors.affiliation: EA 4666, UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France; Laboratoire de Thérapie Cellulaire, CHU Amiens Sud, Amiens, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Regnier
authors.affiliation: EA 4666, UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Debuysscher
authors.affiliation: UMR CNRS 5557 Ecologie Microbienne, Université Lyon 1, Villeurbanne, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.affiliation: EA 4666, UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France; Laboratoire de Thérapie Cellulaire, CHU Amiens Sud, Amiens, France.
authors.forename: Hicham
authors.initials: H
authors.lastname: Bouhlal
mesh_terms: D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D060225:Tetraspanin 28 / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C430423:LY9 protein, human; D011994:Recombinant Proteins; D000071176:Signaling Lymphocytic Activation Molecule Family; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins