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  • Title: An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.
    Author: 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 Rep; 2024 Oct; 25(10):4311-4336. PubMed ID: 39232200.
    Abstract:
    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.
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