A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses

Eloi R. Verrier Che C. Colpitts Charlotte Bach Laura Heydmann 1 Amélie Weiss 2 Mickaël Renaud Sarah C. Durand François Habersetzer 1 David Durantel 3 Georges Abou-Jaoudé Maria M. López Ledesma Daniel J. Felmlee Magali Soumillon Tom Croonenborghs Nathalie Pochet Michael Nassal 4 Catherine Schuster 1 Laurent Brino 2 Camille Sureau 5 Mirjam B. Zeisel Thomas F. Baumert 6, 7
1 Interactions Virus-Hôte et Maladies Hépatiques
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 CRCL - Centre de Recherche en Cancérologie de Lyon
4 University Hospital Freiburg
5 INTS - Institut National de la Transfusion Sanguine [Paris]
6 Service d’Hépatogastroentérologie, NHC, CHU de Strasbourg
7 IVH - Institut de Recherche sur les Maladies Virales et Hépatiques
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
Keywords : Viruses Virus Internalization Untranslated therapy RNA Interference RNA Proteins Belgium Liver Infection Humans Hepatocytes Hepatitis Delta Virus pathogenicity physiology Medicine Carcinoma Cell Division Cells Culture Cultured France Genomics Germany Glypicans Growth Hepatitis Hepatitis B Hepatitis B virus
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Journal articles
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https://hal-univ-lyon1.archives-ouvertes.fr/hal-01796197
Contributor : Lauriane Pillet <>
Submitted on : Saturday, May 19, 2018 - 11:34:31 AM
Last modification on : Tuesday, November 19, 2019 - 2:42:09 AM

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UNIV-LYON1 | CNRS | IGBMC | SITE-ALSACE | CRCL | U1110 | UDL

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Eloi R. Verrier, Che C. Colpitts, Charlotte Bach, Laura Heydmann, Amélie Weiss, et al.. A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses. Hepatology, Wiley-Blackwell, 2016, 63 (1), pp.35-48. ⟨10.1002/hep.28013⟩. ⟨hal-01796197⟩

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