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An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes

Current culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co-infected with the he...

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Main Authors: Chi, Huanting (Author) , Qu, Bingqian (Author) , Prawira, Angga (Author) , Richardt, Talisa (Author) , Maurer, Lars (Author) , Hu, Jungen (Author) , Fu, Rebecca Menhua (Author) , Lempp, Florian A. (Author) , Zhang, Zhenfeng (Author) , Grimm, Dirk (Author) , Wu, Xianfang (Author) , Urban, Stephan (Author) , Dao Thi, Viet Loan (Author)
Format: Article (Journal)
Language:English
Published: October 10, 2024
In: EMBO reports
Year: 2024, Volume: 25, Issue: 10, Pages: 4311-4336
ISSN:1469-3178
DOI:10.1038/s44319-024-00236-0
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44319-024-00236-0
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.1038/s44319-024-00236-0
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Author Notes:Huanting Chi, Bingqian Qu, Angga Prawira, Talisa Richardt, Lars Maurer, Jungen Hu, Rebecca M Fu, Florian A Lempp, Zhenfeng Zhang, Dirk Grimm, Xianfang Wu, Stephan Urban & Viet Loan Dao Thi
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Summary:Current culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co-infected with the helper hepatitis B virus (HBV) or transduced to express the HBV envelope protein HBsAg, HLCs effectively release infectious progeny virions. We also show that HBsAg-expressing HLCs support the extracellular spread of HDV, thus providing a valuable platform for testing available anti-HDV regimens. By challenging the cells along the differentiation with HDV infection, we have identified CD63 as a potential HDV co-entry factor that was rate-limiting for HDV infection in immature hepatocytes. Given their renewable source and the potential to derive hPSCs from individual patients, we propose HLCs as a promising model for investigating HDV biology. Our findings offer new insights into HDV infection and expand the repertoire of research tools available for the development of therapeutic interventions.
Item Description:Online: 04. September 2024
Gesehen am 17.10.2024
Physical Description:Online Resource
ISSN:1469-3178
DOI:10.1038/s44319-024-00236-0

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