Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection
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 ofte...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.809774/full |
| _version_ | 1818977731842408448 |
|---|---|
| author | Mara Schwerdtfeger Julia Dickow Yasmin Schmitz Sandra Francois Zehra Karakoese Zehra Karakoese Anna Malyshkina Torben Knuschke Ulf Dittmer Ulf Dittmer Kathrin Sutter Kathrin Sutter |
| author_facet | Mara Schwerdtfeger Julia Dickow Yasmin Schmitz Sandra Francois Zehra Karakoese Zehra Karakoese Anna Malyshkina Torben Knuschke Ulf Dittmer Ulf Dittmer Kathrin Sutter Kathrin Sutter |
| author_sort | Mara Schwerdtfeger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T16:32:24Z |
| format | Article |
| id | doaj.art-6e632670a1494f1aa74e3e95bb636a60 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T16:32:24Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6e632670a1494f1aa74e3e95bb636a602022-12-21T19:33:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.809774809774Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral InfectionMara Schwerdtfeger0Julia Dickow1Yasmin Schmitz2Sandra Francois3Zehra Karakoese4Zehra Karakoese5Anna Malyshkina6Torben Knuschke7Ulf Dittmer8Ulf Dittmer9Kathrin Sutter10Kathrin Sutter11Institute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Translational HIV Research, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Translational HIV Research, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University of Duisburg-Essen, Essen, GermanyInstitute for Translational HIV Research, University of Duisburg-Essen, Essen, GermanyType 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.809774/fullType I IFNsretroviral infectionFriend retroviruspersistent infectionimmunotherapycytotoxic CD8+ T cells |
| spellingShingle | Mara Schwerdtfeger Julia Dickow Yasmin Schmitz Sandra Francois Zehra Karakoese Zehra Karakoese Anna Malyshkina Torben Knuschke Ulf Dittmer Ulf Dittmer Kathrin Sutter Kathrin Sutter Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection Frontiers in Immunology Type I IFNs retroviral infection Friend retrovirus persistent infection immunotherapy cytotoxic CD8+ T cells |
| title | Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection |
| title_full | Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection |
| title_fullStr | Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection |
| title_full_unstemmed | Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection |
| title_short | Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection |
| title_sort | immunotherapy with interferon α11 but not interferon beta controls persistent retroviral infection |
| topic | Type I IFNs retroviral infection Friend retrovirus persistent infection immunotherapy cytotoxic CD8+ T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.809774/full |
| work_keys_str_mv | AT maraschwerdtfeger immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT juliadickow immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT yasminschmitz immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT sandrafrancois immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT zehrakarakoese immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT zehrakarakoese immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT annamalyshkina immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT torbenknuschke immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT ulfdittmer immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT ulfdittmer immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT kathrinsutter immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection AT kathrinsutter immunotherapywithinterferona11butnotinterferonbetacontrolspersistentretroviralinfection |