P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response
Poxins are poxviral proteins that act by degrading 2´3´-cGAMP, a key molecule of cGAS-STING axis that drives and amplifies the antiviral response. Previous works have described some poxin homologous among lepidopteran and baculoviral genes. In particular, P26, a poxin homologous from AcMNPV retains...
| Autores principales: | , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Springer
2023
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| Acceso en línea: | http://hdl.handle.net/20.500.12123/15111 https://link.springer.com/article/10.1007/s00253-023-12703-0 https://doi.org/10.1007/s00253-023-12703-0 |
| _version_ | 1855485492718469120 |
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| author | Amalfi, Sabrina Plastine, María Del Pilar Lopez, Maria Gabriela Gravisaco, María José Taboga, Oscar Alberto Alfonso, Victoria |
| author_browse | Alfonso, Victoria Amalfi, Sabrina Gravisaco, María José Lopez, Maria Gabriela Plastine, María Del Pilar Taboga, Oscar Alberto |
| author_facet | Amalfi, Sabrina Plastine, María Del Pilar Lopez, Maria Gabriela Gravisaco, María José Taboga, Oscar Alberto Alfonso, Victoria |
| author_sort | Amalfi, Sabrina |
| collection | INTA Digital |
| description | Poxins are poxviral proteins that act by degrading 2´3´-cGAMP, a key molecule of cGAS-STING axis that drives and amplifies the antiviral response. Previous works have described some poxin homologous among lepidopteran and baculoviral genes. In particular, P26, a poxin homologous from AcMNPV retains the 2´3´-cGAMP degradation activity in vitro. In this work, we demonstrated that the antiviral activity triggered by baculovirus was disrupted by the transient expression of P26 in murine and human cell lines, and the effect of this action is not only on IFN-β production but also on the induction of IFN-λ. Besides, we proved P26 functionality in a stable-transformed cell line where the protein was constitutively expressed, preventing the production of IFN-β induced by baculovirus and resulting in an improvement in the transduction efficiency by the attenuation of the antiviral activity. Finally, we incorporated P26 into budded virions by capsid display or passive incorporation, and the results showed that both strategies resulted in an improvement of 3–17 times in the efficiency of transgene expression in murine fibroblasts. Our results suggest that the incorporation of P26 to budded baculoviral vectors is a very promising tool to modulate negatively the innate antiviral cellular response and to improve the efficiency of gene delivery in mammalian cells. |
| format | Artículo |
| id | INTA15111 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Springer |
| publisherStr | Springer |
| record_format | dspace |
| spelling | INTA151112023-09-05T16:31:22Z P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response Amalfi, Sabrina Plastine, María Del Pilar Lopez, Maria Gabriela Gravisaco, María José Taboga, Oscar Alberto Alfonso, Victoria Baculovirus Viricidas Antiviral Agents Poxins are poxviral proteins that act by degrading 2´3´-cGAMP, a key molecule of cGAS-STING axis that drives and amplifies the antiviral response. Previous works have described some poxin homologous among lepidopteran and baculoviral genes. In particular, P26, a poxin homologous from AcMNPV retains the 2´3´-cGAMP degradation activity in vitro. In this work, we demonstrated that the antiviral activity triggered by baculovirus was disrupted by the transient expression of P26 in murine and human cell lines, and the effect of this action is not only on IFN-β production but also on the induction of IFN-λ. Besides, we proved P26 functionality in a stable-transformed cell line where the protein was constitutively expressed, preventing the production of IFN-β induced by baculovirus and resulting in an improvement in the transduction efficiency by the attenuation of the antiviral activity. Finally, we incorporated P26 into budded virions by capsid display or passive incorporation, and the results showed that both strategies resulted in an improvement of 3–17 times in the efficiency of transgene expression in murine fibroblasts. Our results suggest that the incorporation of P26 to budded baculoviral vectors is a very promising tool to modulate negatively the innate antiviral cellular response and to improve the efficiency of gene delivery in mammalian cells. Instituto de Biotecnología Fil: Amalfi, Sabrina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Amalfi, Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Plastine, María Del Pilar. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Plastine, María Del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lopez, Maria Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Lopez, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Taboga, Oscar Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Taboga, Oscar Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Alfonso, Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Alfonso, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2023-09-05T16:15:18Z 2023-09-05T16:15:18Z 2023-08 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/15111 https://link.springer.com/article/10.1007/s00253-023-12703-0 1432-0614 https://doi.org/10.1007/s00253-023-12703-0 eng info:eu-repograntAgreement/INTA/2019-PD-E5-I105-001, Patógenos animales: su interacción con el hospedador y el medio ambiente. Impacto en productividad, ecosistemas, sanidad animal y salud pública en el marco ?Una Salud? info:eu-repo/semantics/restrictedAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Springer Applied Microbiology and Biotechnology (Published: 14 August 2023) |
| spellingShingle | Baculovirus Viricidas Antiviral Agents Amalfi, Sabrina Plastine, María Del Pilar Lopez, Maria Gabriela Gravisaco, María José Taboga, Oscar Alberto Alfonso, Victoria P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| title | P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| title_full | P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| title_fullStr | P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| title_full_unstemmed | P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| title_short | P26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| title_sort | p26 enhances baculovirus gene delivery by modulating the mammalian antiviral response |
| topic | Baculovirus Viricidas Antiviral Agents |
| url | http://hdl.handle.net/20.500.12123/15111 https://link.springer.com/article/10.1007/s00253-023-12703-0 https://doi.org/10.1007/s00253-023-12703-0 |
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