000K utf8 1100 2022$c2022-01-20 1500 eng 2050 urn:nbn:de:hbz:465-20220804-121307-2 2051 10.3389/fimmu.2021.809774 3000 Schwerdtfeger, Mara 3010 Dickow, Julia 3010 Dittmer, Ulf 3010 Francois, Sandra 3010 Karakoese, Zehra 3010 Knuschke, Torben 3010 Malyshkina, Anna 3010 Schmitz, Yasmin 3010 Sutter, Kathrin 4000 Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection. [Schwerdtfeger, Mara] 4209 Type I Interferons (IFNs), including numerous IFNα subtypes and IFNβ, are key molecules during innate and adaptive immune responses against viral infections. These cytokines exert various non-redundant biological activities, although binding to the same receptor. Persistent viral infections are often characterized by increased IFN signatures implicating a potential role of type I IFNs in disease pathogenesis. Using the well-established Friend retrovirus (FV) mouse model, we compared the therapeutic efficacy of IFNα11 and IFNβ in acute and chronic retroviral infection. We observed a strong antiviral activity of both IFNs during acute FV infection, whereas only IFNα11 and not IFNβ could also control persistent FV infection. The therapeutic treatment with IFNα11 induced the expression of antiviral IFN-stimulated genes (ISG) and improved cytotoxic T cell responses. Finally, dysfunctional CD8+ T cells solely regained cytotoxicity after IFNα11 treatment. Our data provide evidence for opposing activities of type I IFNs during chronic retroviral infections. IFNβ was shown to be involved in immune dysfunction in chronic infections, whereas IFNα11 had a strong antiviral potential and reactivated exhausted T cells during persistent retroviral infection. In contrast, during acute infection, both type I IFNs were able to efficiently suppress FV replication. 4950 https://doi.org/10.3389/fimmu.2021.809774$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:hbz:465-20220804-121307-2$xR$3Volltext$534 4961 https://duepublico2.uni-due.de/receive/duepublico_mods_00076415 5051 610 5550 Animals 5550 Antiviral Agents 5550 Biomarkers 5550 Cell Line 5550 Cytotoxic Cd8+ T Cells 5550 Cytotoxicity, Immunologic 5550 Disease Management 5550 Disease Models, Animal 5550 Female 5550 Friend murine leukemia virus 5550 Friend Retrovirus 5550 Host-Pathogen Interactions 5550 Immunologic Factors 5550 Immunotherapy 5550 Interferon-alpha 5550 Interferon-beta 5550 Interferon Type I 5550 Leukemia Virus, Murine 5550 Lymphocytes 5550 Mice 5550 Persistent infection 5550 Retroviral Infection 5550 Retroviridae Infections 5550 Treatment Outcome 5550 Type I Ifns 5550 Viral Load 5550 Virus Replication