biostudies-literatureUnknown28(9)Keller FGerman Research FoundationNatural 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 <i>IFITM3</i>, <i>IRF1</i>, <i>IFIT2,</i> and <i>ISG20</i> 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 constituiScience113216https://www.ebi.ac.uk/biostudies/studies/S-EPMC12362017biostudies-literatureDifferentiation-associated ISG expression of NK cells in chronic viral infection.PMC12362017Sogukpinar ORizzi MEils RThimme RHofmann MLohmann VBoettler TBengsch BBeier FBauersfeld LSagarNeumann-Haefelin CBinder MKeller FTrefzer TJechow KRusignuolo GPichlmair AConrad CChua RLfalseDifferentiation-associated ISG expression of NK cells in chronic viral infection.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 <i>IFITM3</i>, <i>IRF1</i>, <i>IFIT2,</i> and <i>ISG20</i> 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 constitu2025-01-01T00:00:00Z2025 Sep2026-07-15T05:56:11.158Z2026-06-30T03:20:22.796ZS-EPMC123620174083723410.1016/j.isci.2025.113216