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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses
Eloi R Verrier1,2, Che C Colpitts1,2, Charlotte Bach1,2
1Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
Unlabelled:
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.
Insights
Researchers identified glypican 5 as a key factor for hepatitis B and D virus entry into liver cells. This discovery advances understanding of viral infections and may lead to new hepatitis therapies.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Chronic hepatitis B and D infections are significant global causes of liver disease and hepatocellular carcinoma.
- Current therapeutic strategies lack curative approaches for these viral infections.
- Hepatitis B and D viruses share envelope proteins and utilize the sodium/taurocholate cotransporting polypeptide as a hepatocyte receptor, but entry mechanisms remain unclear.
Purpose of the Study:
- To elucidate the mechanisms of hepatitis delta virus entry and infection.
- To identify host cell factors involved in hepatitis B and D virus entry.
Main Methods:
- Establishment of a high-throughput infectious cell culture model for hepatitis delta virus.
- Implementation of a targeted RNA interference screen to identify viral entry factors.
Main Results:
- Identification of glypican 5 as a common host cell entry factor for both hepatitis B and delta viruses.
- Demonstration of glypican 5's crucial role in the viral entry process.
Conclusions:
- The findings enhance comprehension of virus-host interactions during cell entry.
- Glypican 5 represents a potential therapeutic target for hepatitis B and D infections.
- Virus-glypican 5 interactions may contribute to the pathogenesis of virus-induced liver disease and cancer.
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