A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses
Résumé
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
Mots clés
Belgium
Liver
Infection
Humans
pathogenicity
physiology
Medicine
Carcinoma
Cell Division
Cells
Culture
Cultured
France
Genomics
Germany
Glypicans
Growth
Hepatitis
Hepatitis B
Hepatitis B virus
Hepatitis Delta Virus
Hepatocytes
Proteins
RNA
RNA Interference
therapy
Untranslated
Virus Internalization
Viruses