@Article{duepublico_mods_00076415, author = {Schwerdtfeger, Mara and Dickow, Julia and Schmitz, Yasmin and Francois, Sandra and Karakoese, Zehra and Malyshkina, Anna and Knuschke, Torben and Dittmer, Ulf and Sutter, Kathrin}, title = {Immunotherapy With Interferon $\alpha$11, But Not Interferon Beta, Controls Persistent Retroviral Infection.}, year = {2022}, month = {Jan}, day = {20}, keywords = {Lymphocytes; Cell Line; Animals; Mice; Leukemia Virus, Murine; Friend murine leukemia virus; Retroviridae Infections; Disease Models, Animal; Interferon Type I; Interferon-alpha; Interferon-beta; Immunologic Factors; Antiviral Agents; Treatment Outcome; Viral Load; Virus Replication; Cytotoxicity, Immunologic; Disease Management; Female; Host-Pathogen Interactions; Biomarkers; Immunotherapy; Persistent infection; Type I Ifns; Retroviral Infection; Cytotoxic Cd8+ T Cells; Friend Retrovirus}, abstract = {Type I Interferons (IFNs), including numerous IFN$\alpha$ subtypes and IFN$\beta$, 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 IFN$\alpha$11 and IFN$\beta$ in acute and chronic retroviral infection. We observed a strong antiviral activity of both IFNs during acute FV infection, whereas only IFN$\alpha$11 and not IFN$\beta$ could also control persistent FV infection. The therapeutic treatment with IFN$\alpha$11 induced the expression of antiviral IFN-stimulated genes (ISG) and improved cytotoxic T cell responses. Finally, dysfunctional CD8+ T cells solely regained cytotoxicity after IFN$\alpha$11 treatment. Our data provide evidence for opposing activities of type I IFNs during chronic retroviral infections. IFN$\beta$ was shown to be involved in immune dysfunction in chronic infections, whereas IFN$\alpha$11 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.}, note = {<p>Schwerdtfeger M, Dickow J, Schmitz Y, Francois S, Karakoese Z, Malyshkina A, Knuschke T, Dittmer U and Sutter K (2022) Immunotherapy With Interferon $\alpha$11, But Not Interferon Beta, Controls Persistent Retroviral Infection. <em>Front. Immunol.</em> 12:809774. <a href="https://doi.org/10.3389/fimmu.2021.809774">https://doi.org/10.3389/fimmu.2021.809774</a></p> <p>Published: 20 January 2022</p>}, note = {Version of Record / Verlagsversion}, note = {The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.}, doi = {10.3389/fimmu.2021.809774}, url = {https://duepublico2.uni-due.de/receive/duepublico_mods_00076415}, url = {https://doi.org/10.3389/fimmu.2021.809774}, file = {:https://duepublico2.uni-due.de/servlets/MCRFileNodeServlet/duepublico_derivate_00076146/fimmu_2022-12-809774.pdf:PDF}, language = {en} }