.png){kind=icon}
.png){kind=icon}
Return
An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes
.png){kind=icon}
OA
AI
DOI：10.1038/s44319-024-00236-0.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
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. This study presents human pluripotent stem cell-derived hepatocyte-like cells (HLCs) as a culture system that expands the repertoire of research tools for studying hepatitis B and D viruses (HBV/HDV) and identifies CD63 as a potential HDV co-entry factor.Co-infection with HBV or virus-mediated delivery of HBV surface proteins enables HDV to complete its life cycle in HLCs.Extracellular HDV spread in HLCs enables the evaluation of anti-HDV therapies.HDV permissiveness along HLC differentiation reveals CD63 as a novel co-factor of HDV cell entry. This study presents human pluripotent stem cell-derived hepatocyte-like cells (HLCs) as a culture system that expands the repertoire of research tools for studying hepatitis B and D viruses (HBV/HDV) and identifies CD63 as a potential HDV co-entry factor.
Keywords:
Hepatitis D Virus
Hepatitis B Virus
Human Pluripotent Stem Cells
Hepatocyte-like Cells
Antiviral Treatment
Journal
E
IF:
6.2
Papers:
6.4K
Citations:
2.1W