title: A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses.
abstract: Chronic hepatitis B and D infections are major causes of liver disease and hepatocellular carcinoma worldwide. Efficient therapeutic approaches for cure are absent. Sharing the same envelope proteins, hepatitis B virus and hepatitis delta virus use the sodium/taurocholate cotransporting polypeptide (a bile acid transporter) as a receptor to enter hepatocytes. However, the detailed mechanisms of the viral entry process are still poorly understood. Here, we established a high-throughput infectious cell culture model enabling functional genomics of hepatitis delta virus entry and infection. Using a targeted RNA interference entry screen, we identified glypican 5 as a common host cell entry factor for hepatitis B and delta viruses.
  
  
  CONCLUSIONS
  These findings advance our understanding of virus cell entry and open new avenues for curative therapies. As glypicans have been shown to play a role in the control of cell division and growth regulation, virus-glypican 5 interactions may also play a role in the pathogenesis of virus-induced liver disease and cancer.
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Eloi R
authors.initials: ER
authors.lastname: Verrier
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Che C
authors.initials: CC
authors.lastname: Colpitts
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bach
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Heydmann
authors.affiliation: IGBMC, Plateforme de Criblage Haut-débit, Illkirch, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Weiss
authors.affiliation: IGBMC, Plateforme de Criblage Haut-débit, Illkirch, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Renaud
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Durand
authors.affiliation: Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Habersetzer
authors.affiliation: Inserm, U1052, CNRS UMR 5286, Cancer Research Center of Lyon, Université de Lyon, Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Durantel
authors.affiliation: INTS, Laboratoire de Virologie Moléculaire, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Abou-Jaoudé
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Maria M
authors.initials: MM
authors.lastname: López Ledesma
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Felmlee
authors.affiliation: Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.
authors.forename: Magali
authors.initials: M
authors.lastname: Soumillon
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.|KU Leuven Technology Campus Geel, AdvISe, Geel, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Croonenborghs
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pochet
authors.affiliation: Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nassal
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schuster
authors.affiliation: IGBMC, Plateforme de Criblage Haut-débit, Illkirch, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brino
authors.affiliation: INTS, Laboratoire de Virologie Moléculaire, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Sureau
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.affiliation: Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.|Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D002478:Cells, Cultured; D053673:Glypicans / Q000502:physiology*; D006515:Hepatitis B virus / Q000472:pathogenicity*; D003698:Hepatitis Delta Virus / Q000472:pathogenicity*; D006801:Humans; D022661:RNA, Untranslated / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D053673:Glypicans; D022661:RNA, Untranslated