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

Autor:	Chi H; Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.; German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany., Qu B; Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.; Molecular Virology, Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.; Division of Veterinary Medicine, Paul-Ehrlich-Institut, Langen, Germany., Prawira A; Molecular Virology, Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany., Richardt T; Molecular Virology, Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany., Maurer L; Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.; Department of Infectious Diseases, Virology, Section Viral Vector Technologies, University Hospital Heidelberg, Cluster of Excellence CellNetworks, BioQuant, Center for Integrative Infectious Diseases Research (CIID), Heidelberg, Germany., Hu J; Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany., Fu RM; Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany., Lempp FA; Molecular Virology, Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.; Humabs Biomed SA, A Subsidiary of Vir Biotechnology, Bellinzona, Switzerland., Zhang Z; Molecular Virology, Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.; School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Grimm D; German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany.; Department of Infectious Diseases, Virology, Section Viral Vector Technologies, University Hospital Heidelberg, Cluster of Excellence CellNetworks, BioQuant, Center for Integrative Infectious Diseases Research (CIID), Heidelberg, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg, Heidelberg, Germany., Wu X; Infection Biology Program and Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA., Urban S; German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany. Stephan.Urban@med.uni-heidelberg.de.; Molecular Virology, Department of Infectious Diseases, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany. Stephan.Urban@med.uni-heidelberg.de., Dao Thi VL; Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany. VietLoan.DaoThi@med.uni-heidelberg.de.; German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany. VietLoan.DaoThi@med.uni-heidelberg.de.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Oct; Vol. 25 (10), pp. 4311-4336. Date of Electronic Publication: 2024 Sep 04.
DOI:	10.1038/s44319-024-00236-0
Abstrakt:	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).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu