Differentiation-associated ISG expression of NK cells in chronic viral infection
Summary: Natural killer (NK) cell responses are modulated by type-I interferons (IFNs) in viral infection. Chronic hepatitis C virus (HCV) infection, marked by robust IFN signatures, shows NK cells with reduced cytokine release but heightened cytotoxicity. Comparable alterations occur in chronic hep...
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Elsevier
2025-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225014774 |
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| author | Franziska Keller Robert Lorenz Chua Timo Trefzer Katharina Jechow Liane Bauersfeld Fabian Beier Sagar Özlem Sogukpinar Giuseppe Rusignuolo Marta Rizzi Roland Eils Andreas Pichlmair Marco Binder Bertram Bengsch Christoph Neumann-Haefelin Volker Lohmann Tobias Boettler Christian Conrad Robert Thimme Maike Hofmann |
| author_facet | Franziska Keller Robert Lorenz Chua Timo Trefzer Katharina Jechow Liane Bauersfeld Fabian Beier Sagar Özlem Sogukpinar Giuseppe Rusignuolo Marta Rizzi Roland Eils Andreas Pichlmair Marco Binder Bertram Bengsch Christoph Neumann-Haefelin Volker Lohmann Tobias Boettler Christian Conrad Robert Thimme Maike Hofmann |
| author_sort | Franziska Keller |
| collection | DOAJ |
| description | Summary: Natural killer (NK) cell responses are modulated by type-I interferons (IFNs) in viral infection. Chronic hepatitis C virus (HCV) infection, marked by robust IFN signatures, shows NK cells with reduced cytokine release but heightened cytotoxicity. Comparable alterations occur in chronic hepatitis B virus (HBV) infection even without a pronounced IFN milieu, implying additional regulatory layers. We analyzed NK cells from healthy donors and patients with chronic HBV or HCV and found conserved expression patterns of interferon-stimulated genes (ISGs) such as IFITM3, IRF1, IFIT2, and ISG20 that correlated with NK cell differentiation state. These genes are governed by fate-determining transcription factors, including ETS1, FLI1, and Eomes, and appear to be constitutively expressed rather than driven by persistent IFN exposure. Network analysis suggested that NK cell ISGs participate not only in antiviral defense but also in processes such as transport and metabolism, underscoring their role in shaping NK responses during health and chronic viral infection. |
| format | Article |
| id | doaj-art-7131cd4a2e874af38aa2b1f1637462f7 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-7131cd4a2e874af38aa2b1f1637462f72025-08-20T03:38:19ZengElsevieriScience2589-00422025-09-0128911321610.1016/j.isci.2025.113216Differentiation-associated ISG expression of NK cells in chronic viral infectionFranziska Keller0Robert Lorenz Chua1Timo Trefzer2Katharina Jechow3Liane Bauersfeld4Fabian Beier5 Sagar6Özlem Sogukpinar7Giuseppe Rusignuolo8Marta Rizzi9Roland Eils10Andreas Pichlmair11Marco Binder12Bertram Bengsch13Christoph Neumann-Haefelin14Volker Lohmann15Tobias Boettler16Christian Conrad17Robert Thimme18Maike Hofmann19Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Baden-Württemberg, GermanyCenter for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10178 Berlin, GermanyCenter for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10178 Berlin, GermanyCenter for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10178 Berlin, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, Baden-Württemberg, GermanyTechnical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Bavaria, Germany; German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Bavaria, GermanyResearch Group “Dynamics of Early Viral Infection and the Innate Antiviral Response”, Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center, 69120 Heidelberg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Section Virus-Host-Interactions, University of Heidelberg, Heidelberg, Germany; German Centre for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyCenter for Digital Health, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10178 Berlin, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Medical Center- University of Freiburg, 79106 Freiburg, Baden-Württemberg, Germany; Corresponding authorSummary: Natural killer (NK) cell responses are modulated by type-I interferons (IFNs) in viral infection. Chronic hepatitis C virus (HCV) infection, marked by robust IFN signatures, shows NK cells with reduced cytokine release but heightened cytotoxicity. Comparable alterations occur in chronic hepatitis B virus (HBV) infection even without a pronounced IFN milieu, implying additional regulatory layers. We analyzed NK cells from healthy donors and patients with chronic HBV or HCV and found conserved expression patterns of interferon-stimulated genes (ISGs) such as IFITM3, IRF1, IFIT2, and ISG20 that correlated with NK cell differentiation state. These genes are governed by fate-determining transcription factors, including ETS1, FLI1, and Eomes, and appear to be constitutively expressed rather than driven by persistent IFN exposure. Network analysis suggested that NK cell ISGs participate not only in antiviral defense but also in processes such as transport and metabolism, underscoring their role in shaping NK responses during health and chronic viral infection.http://www.sciencedirect.com/science/article/pii/S2589004225014774ImmunologyTranscriptomics |
| spellingShingle | Franziska Keller Robert Lorenz Chua Timo Trefzer Katharina Jechow Liane Bauersfeld Fabian Beier Sagar Özlem Sogukpinar Giuseppe Rusignuolo Marta Rizzi Roland Eils Andreas Pichlmair Marco Binder Bertram Bengsch Christoph Neumann-Haefelin Volker Lohmann Tobias Boettler Christian Conrad Robert Thimme Maike Hofmann Differentiation-associated ISG expression of NK cells in chronic viral infection iScience Immunology Transcriptomics |
| title | Differentiation-associated ISG expression of NK cells in chronic viral infection |
| title_full | Differentiation-associated ISG expression of NK cells in chronic viral infection |
| title_fullStr | Differentiation-associated ISG expression of NK cells in chronic viral infection |
| title_full_unstemmed | Differentiation-associated ISG expression of NK cells in chronic viral infection |
| title_short | Differentiation-associated ISG expression of NK cells in chronic viral infection |
| title_sort | differentiation associated isg expression of nk cells in chronic viral infection |
| topic | Immunology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225014774 |
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