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Inoculation with infectious HEV particles demonstrates that human liver\u2013derived organoids support the full life cycle of HEV infection. By directing organoids toward polarized monolayers in a transwell system, we observed predominantly apical secretion of HEV particles. Genome-wide transcriptomic and tRNAome analyses revealed robust host responses triggered by viral replication. Drug screening in organoids identified brequinar and homoharringtonine as potent HEV inhibitors, which are also effective against the ribavirin resistance variant harboring G1634R mutation. Thus, successful recapitulation of HEV infection in liver-derived organoids shall facilitate the study of virus-host interactions and development of antiviral therapies.<\/jats:p>","DOI":"10.1126\/sciadv.abj5908","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T18:59:26Z","timestamp":1642618766000},"source":"Crossref","is-referenced-by-count":69,"title":["Recapitulating hepatitis E virus\u2013host interactions and facilitating antiviral drug discovery in human liver\u2013derived organoids"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-4573","authenticated-orcid":true,"given":"Pengfei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3700-1766","authenticated-orcid":true,"given":"Yijin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4434-3120","authenticated-orcid":true,"given":"Jiaye","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla","family":"Lavrijsen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9908-6673","authenticated-orcid":true,"given":"Monique M. 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