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

Hepatology. 2016 Jan;63(1):35-48. doi: 10.1002/hep.28013. Epub 2015 Oct 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Glypicans / physiology*
  • Hepatitis B virus / pathogenicity*
  • Hepatitis Delta Virus / pathogenicity*
  • Humans
  • RNA, Untranslated / physiology*
  • Virus Internalization*


  • Glypicans
  • RNA, Untranslated