{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:36:48Z","timestamp":1771263408316,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human pluripotent stem cell (hPSC)\u2010derived hepatocyte\u2010like cells (HLCs) are a valuable model to investigate host\u2010pathogen interactions of hepatitis viruses in a mature and authentic environment. Here, we investigate the susceptibility of HLCs to the hepatitis delta virus (HDV).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We differentiated hPSC into HLCs, and inoculated them with infectious HDV produced in Huh7<jats:sup>NTCP<\/jats:sup>. HDV infection and cellular response was monitored by RTqPCR and immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cells undergoing hepatic differentiation become susceptible to HDV after acquiring expression of the viral receptor Na<jats:sup>+<\/jats:sup>\u2010taurocholate co\u2010transporting polypeptide (NTCP) during hepatic specification. Inoculation of HLCs with HDV leads to detection of intracellular HDV RNA and accumulation of the HDV antigen in the cells. Upon infection, the HLCs mounted an innate immune response based on induction of the interferons IFNB and L, and upregulation of interferon\u2010stimulated genes. The intensity of this immune response positively correlated with the level of viral replication and was dependant on both the JAK\/STAT and NF\u03baB pathway activation. Importantly, this innate immune response did not inhibit HDV replication. However, pre\u2010treatment of the HLCs with IFN\u03b12b reduced viral infection, suggesting that ISGs may limit early stages of infection. Myrcludex efficiently abrogated infection and blocked innate immune activation. Lonafarnib treatment of HDV mono infected HLCs on the other hand led to exacerbated viral replication and innate immune response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The HDV in vitro mono\u2010infection model represents a new tool to study HDV replication, its host\u2010pathogen interactions and evaluate new antiviral drugs in cells displaying mature hepatic functions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15655","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T08:13:46Z","timestamp":1687853626000},"page":"2116-2129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hepatitis D virus infection, innate immune response and antiviral treatments in stem cell\u2010derived hepatocytes"],"prefix":"10.1111","volume":"43","author":[{"given":"Frauke","family":"Lange","sequence":"first","affiliation":[{"name":"Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between Medical School Hannover (MHH) and Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Garn","sequence":"additional","affiliation":[{"name":"Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between Medical School Hannover (MHH) and Helmholtz Centre for Infection Research (HZI)  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holda A.","family":"Anagho","sequence":"additional","affiliation":[{"name":"Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between Medical School Hannover (MHH) and Helmholtz Centre for Infection Research (HZI)  Hannover Germany"},{"name":"Institut f\u00fcr Molekularbiologie, Medizinische Hochschule Hannover  Hannover Germany"},{"name":"Klinik f\u00fcr Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian W. 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