{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:38:28Z","timestamp":1790836708302,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T00:00:00Z","timestamp":1637366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR179"],"award-info":[{"award-number":["TRR179"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR338"],"award-info":[{"award-number":["TRR338"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmholtz-Gemeinschaft, Impuls- und Vernetzungsfonds","award":["PD-318"],"award-info":[{"award-number":["PD-318"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Approximately 70 million humans worldwide are affected by chronic hepatitis D, which rapidly leads to liver cirrhosis and hepatocellular carcinoma due to chronic inflammation. The triggers and consequences of this chronic inflammation, induced by co-infection with the hepatitis D virus (HDV) and the hepatitis B virus (HBV), are poorly understood. Using CRISPR technology, we characterized the recognition of HDV mono- and co-infection by intracellular innate immunity and determined its influence on the viral life cycle and effector T-cell responses using different HBV and HDV permissive hepatoma cell lines. We showed that HDV infection is detected by MDA5 and -after a lag phase -induces a profound type I interferon response in the infected cells. The type I interferon response, however, was not able to suppress HDV replication or spread, thus providing a persistent trigger. Using engineered T-cells directed against the envelope proteins commonly used by HBV and HDV, we found that HDV immune recognition enhanced T-cell cytotoxicity. Interestingly, the T-cell effector function was enhanced independently of antigen presentation. These findings help to explain immune mediated tissue damage in chronic hepatitis D patients and indicate that combining innate triggers with T-cell activating therapies might allow for a curative approach.<\/jats:p>","DOI":"10.3390\/cells10113253","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"3253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatitis-D Virus Infection Is Not Impaired by Innate Immunity but Increases Cytotoxic T-Cell Activity"],"prefix":"10.3390","volume":"10","author":[{"given":"Sebastian Maximilian","family":"Altstetter","sequence":"first","affiliation":[{"name":"Institute of Virology, School of Medicine, Helmholtz Zentrum M\u00fcnchen\/Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Quitt","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Helmholtz Zentrum M\u00fcnchen\/Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-9663","authenticated-orcid":false,"given":"Francesca","family":"Pinci","sequence":"additional","affiliation":[{"name":"Gene Center and Department of Biochemistry, Ludwig-Maximilians\u2014University Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Hornung","sequence":"additional","affiliation":[{"name":"Gene Center and Department of Biochemistry, Ludwig-Maximilians\u2014University Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron Michael","family":"Lucko","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Helmholtz Zentrum M\u00fcnchen\/Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Wisskirchen","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Helmholtz Zentrum M\u00fcnchen\/Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-9358","authenticated-orcid":false,"given":"Stephanie","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Helmholtz Zentrum M\u00fcnchen\/Technical University of Munich, 81675 Munich, Germany"},{"name":"Institute of Cardiovascular Immunology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-1911","authenticated-orcid":false,"given":"Ulrike","family":"Protzer","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Helmholtz Zentrum M\u00fcnchen\/Technical University of Munich, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1053\/j.gastro.2018.09.058","article-title":"Pathogenesis of and New Therapies for Hepatitis D","volume":"156","author":"Koh","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1136\/gutjnl-2020-323888","article-title":"Hepatitis D virus in 2021: Virology, immunology and new treatment approaches for a difficult-to-treat disease","volume":"70","author":"Urban","year":"2021","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2147\/JEP.S235550","article-title":"Experimental Drugs for the Treatment of Hepatitis D","volume":"13","author":"Sandmann","year":"2021","journal-title":"J. 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