An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes
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. © 2024. The Author(s).
| Authors | Chi H, Qu B, Prawira A, Richardt T, Maurer L, Hu J, Fu RM, Lempp FA, Zhang Z, Grimm D, Wu X, Urban S, Dao Thi VL |
|---|---|
| Journal | EMBO reports |
| Publication Date | 2024 Oct;25(10):4311-4336 |
| PubMed | 39232200 |
| PubMed Central | PMC11466959 |
| DOI | 10.1038/s44319-024-00236-0 |