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As natural killer (NK) cells play an important role during the natural course of acute HCV, we assessed the NK cell compartment via flow cytometry and single-cell sequencing in longitudinally sampled patients with acute HCV and compared this to healthy controls and patients with chronic HCV. At the transcriptomic level, we identified a subset of highly activated NK cells with a robust type I interferon imprint. While the population of activated NK cells vanished after DAA-mediated cure, a long-term phenotypic imprint of infection was observed in comparison to healthy controls. Collectively, these data suggest an interferon-driven rise of an activated NK cell population during acute hepatitis C that is largely restored upon viral clearance. This study provides insights into the immunological basis for successful antiviral response to hepatitis C.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf654","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T12:52:58Z","timestamp":1766494378000},"page":"e1330-e1340","source":"Crossref","is-referenced-by-count":0,"title":["Transient Interferon-Driven Natural Killer Cell Activation in Acute Hepatitis C"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9974-6133","authenticated-orcid":false,"given":"Benedikt","family":"Strunz","sequence":"first","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyao","family":"Zhan","sequence":"additional","affiliation":[{"name":"Centre for Individualised Infection Medicine (CIIM), Helmholtz-Centre 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