دورية أكاديمية
Interferon-γ inducible factor 16 (IFI16) restricts adeno-associated virus type 2 (AAV2) transduction in an immune-modulatory independent way
| العنوان: | Interferon-γ inducible factor 16 (IFI16) restricts adeno-associated virus type 2 (AAV2) transduction in an immune-modulatory independent way |
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| المؤلفون: | Sutter, Sereina O, Tobler, Kurt, Seyffert, Michael, Lkharrazi, Anouk, Zöllig, Joël, Schraner, Elisabeth M, Vogt, Bernd, Büning, Hildegard, Fraefel, Cornel |
| المساهمون: | Banks, Lawrence, Banks, L ( Lawrence ) |
| المصدر: | Sutter, Sereina O; Tobler, Kurt; Seyffert, Michael; Lkharrazi, Anouk; Zöllig, Joël; Schraner, Elisabeth M; Vogt, Bernd; Büning, Hildegard; Fraefel, Cornel (2024). Interferon-γ inducible factor 16 (IFI16) restricts adeno-associated virus type 2 (AAV2) transduction in an immune-modulatory independent way. Journal of Virology:Epub ahead of print. |
| بيانات النشر: | American Society for Microbiology |
| سنة النشر: | 2024 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Institute of Virology, 570 Life sciences, biology |
| الوصف: | We determined the transcription profile of adeno-associated virus type 2 (AAV2)-infected primary human fibroblasts. Subsequent analysis revealed that cells respond to AAV infection through changes in several significantly affected pathways, including cell cycle regulation, chromatin modulation, and innate immune responses. Various assays were performed to validate selected differentially expressed genes and to confirm not only the quality but also the robustness of the raw data. One of the genes upregulated in AAV2-infected cells was interferon-γ inducible factor 16 (IFI16). IFI16 is known as a multifunctional cytosolic and nuclear innate immune sensor for double-stranded as well as single-stranded DNA, exerting its effects through various mechanisms, such as interferon response, epigenetic modifications, or transcriptional regulation. IFI16 thereby constitutes a restriction factor for many different viruses among them, as shown here, AAV2 and thereof derived vectors. Indeed, the post-transcriptional silencing of IFI16 significantly increased AAV2 transduction efficiency, independent of the structure of the virus/vector genome. We also show that IFI16 exerts its inhibitory effect on AAV2 transduction in an immune-modulatory independent way by interfering with Sp1-dependent transactivation of wild-type AAV2 and AAV2 vector promoters. IMPORTANCE Adeno-associated virus (AAV) vectors are among the most frequently used viral vectors for gene therapy. The lack of pathogenicity of the parental virus, the long-term persistence as episomes in non-proliferating cells, and the availability of a variety of AAV serotypes differing in their cellular tropism are advantageous features of this biological nanoparticle. To deepen our understanding of virus-host interactions, especially in terms of antiviral responses, we present here the first transcriptome analysis of AAV serotype 2 (AAV2)-infected human primary fibroblasts. Our findings indicate that interferon-γ inducible factor 16 acts as an antiviral factor in AAV2 infection ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0022-538X |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/260233/1/PU719.pdfTest; info:pmid/38837381; urn:issn:0022-538X |
| DOI: | 10.5167/uzh-260233 |
| DOI: | 10.1128/jvi.00110-24 |
| الإتاحة: | https://doi.org/10.5167/uzh-26023310.1128/jvi.00110-24Test https://www.zora.uzh.ch/id/eprint/260233Test/ https://www.zora.uzh.ch/id/eprint/260233/1/PU719.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.42ADE50D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 0022538X |
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| DOI: | 10.5167/uzh-260233 |