A targeted functional RNAi screen uncovers Glypican 5 as an entry factor for hepatitis B and D viruses

Verrier, Eloi R; Colpitts, Che C; Bach, Charlotte; Heydmann, Laura; Weiss, Amélie; Renaud, Mickaël; Durand, Sarah C; Habersetzer, François; Durantel, David; Abou-Jaoudé, Georges; López Ledesma, Maria M; Felmlee, Daniel J; Soumillon, Magali; Croonenborghs, Tom; Pochet, Nathalie; Nassal, Michael; Schuster, Catherine; Brino, Laurent; Sureau, Camille; Zeisel, Mirjam B; Baumert, Thomas F

doi:10.1002/hep.28013

A targeted functional RNAi screen uncovers Glypican 5 as an entry factor for hepatitis B and D viruses

Author:

Verrier, Eloi R

Colpitts, Che C ; Bach, Charlotte ; Heydmann, Laura ; Weiss, Amélie ; Renaud, Mickaël ; Durand, Sarah C ; Habersetzer, François ; Durantel, David ; Abou-Jaoudé, Georges ; López Ledesma, Maria M ; Felmlee, Daniel J ; Soumillon, Magali ; Croonenborghs, Tom ; Pochet, Nathalie ; Nassal, Michael ; Schuster, Catherine ; Brino, Laurent ; Sureau, Camille ; Zeisel, Mirjam B ; Baumert, Thomas F

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, HEPARAN-SULFATE, C VIRUS, MEMBRANE TRANSPORTER, CYCLOSPORINE-A, INFECTION, BINDING, HEPATOCYTES, EXPRESSION, INHIBITOR, RECEPTOR, Cells, Cultured, Glypicans, Hepatitis B virus, Hepatitis Delta Virus, Humans, RNA, Untranslated, Virus Internalization, 1101 Medical Biochemistry and Metabolomics, 1103 Clinical Sciences, 1107 Immunology, 3202 Clinical sciences, 3204 Immunology

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 (HBV) and hepatitis D virus (HDV) use the sodium taurocholate co-transporting polypeptide (NTCP, 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 HDV entry and infection. Using a targeted RNAi entry screen we identified glypican 5 (GPC5) as a common host cell entry factor for HBV and HDV.