Transient Interferon-Driven Natural Killer Cell Activation in Acute Hepatitis C
Acute infection with hepatitis C virus (HCV) is a rare event that can be treated successfully with direct-acting antivirals (DAAs). 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.
Authors
- von der Leyen He
- Cheng-jian Xu
- K Sosnowsky
- H. Klinker
- Andreas Umgelter (ORCID: https://orcid.org/0000-0002-3623-180X)
- Susanne Wiebecke
- J. VAN HENGST
- Marc Ringelhan (ORCID: https://orcid.org/0000-0003-3131-5657)
- Annika Niehrs (ORCID: https://orcid.org/0000-0002-2190-4346)
- Marija Janković (ORCID: https://orcid.org/0000-0002-2255-7163)
- Tanvi Khera (ORCID: https://orcid.org/0000-0002-1287-3197)
- Benedikt Strunz (ORCID: https://orcid.org/0000-0001-9974-6133)
- Dorothee von Witzendorff
- Gudrun Hilgard
- Christoph Jochum (ORCID: https://orcid.org/0000-0001-8460-6912)
- Mayr Ug
- Svenja Hardtke (ORCID: https://orcid.org/0000-0002-2913-9001)
- M Cornberg
- Qiuyao Zhan
- Bernhard Schlevogt (ORCID: https://orcid.org/0000-0002-3979-5299)
- Caroline Zöllner (ORCID: https://orcid.org/0000-0002-2215-4815)
- Eckart Schott
- Petra Schulze
- Armin Papkalla
- Niklas Björkström
- Heiner Wedemeyer
- Katja Deterding
- Judith Schrewe
- Anita Pathil
- Christoph D Spinner
- Kerstin Port
- Johannes Wiegand
- Ji-Eun Lee
- Michael P Manns
- the HepNet Acute HCV IV Study Group
- Guido Gerken
- Armin Koch
- Ulrich Spengler
- Stefan Zeuzem
- Kristina Weber
- Julian Schulze zur Wiesch
- Tania M Welzel
- Peter Hoffmann
Institutions
- Karolinska University Hospital (SE)
- Medizinische Hochschule Hannover (DE)
- German Center for Infection Research (DE)
- German Liver Foundation (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2025-12-23
- DOI
- https://doi.org/10.1093/infdis/jiaf654
- Citations
- 1
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.80