1. A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses
- Author
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Eloi R. Verrier, Tom Croonenborghs, Georges Abou-Jaoudé, Daniel J. Felmlee, Nathalie Pochet, Amélie Weiss, Sarah C. Durand, François Habersetzer, Mickael Renaud, Catherine Schuster, Charlotte Bach, Che C. Colpitts, Thomas F. Baumert, Magali Soumillon, Camille Sureau, David Durantel, Laura Heydmann, Mirjam B. Zeisel, Laurent Brino, Michael Nassal, María Mora González López Ledesma, Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Freiburg, Institut National de la Transfusion Sanguine [Paris] (INTS), Service d’Hépatogastroentérologie, NHC, CHU de Strasbourg, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Pillet, Lauriane
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0301 basic medicine ,RNA, Untranslated ,Glypican ,Culture ,Growth ,medicine.disease_cause ,Hepatitis ,Liver disease ,Belgium ,Germany ,pathogenicity ,Cells, Cultured ,Cultured ,Untranslated ,Genomics ,Hepatitis B ,3. Good health ,Liver ,Hepatocellular carcinoma ,Viruses ,Medicine ,RNA Interference ,France ,Hepatitis Delta Virus ,Infection ,Cell Division ,Hepatitis B virus ,Cells ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Hepatitis B virus PRE beta ,Virus ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Glypicans ,Viral entry ,medicine ,Humans ,therapy ,Hepatology ,Carcinoma ,Proteins ,Virus Internalization ,medicine.disease ,Virology ,030104 developmental biology ,physiology ,Hepatocytes ,RNA - 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. Conclusion: 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. (Hepatology 2016;63:35–48)
- Published
- 2015
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