TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display
Although the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A nove...
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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Wiley
2023
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| Online Access: | http://hdl.handle.net/20.500.12123/15190 https://onlinelibrary.wiley.com/doi/10.1111/imm.13607 https://doi.org/10.1111/imm.13607 |
| _version_ | 1855037262898659328 |
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| author | Molinari, Maria Paula Crespo, Maria Ines Molina, Guido Nicolas Dho, Nicolás D. Marinho, Fábio V. Maletto, Belkys Angélica Leclerc, Claude Oliveira, Sergio C. Taboga, Oscar Alberto Cebrian, Ignacio Moron, Victor Gabriel |
| author_browse | Cebrian, Ignacio Crespo, Maria Ines Dho, Nicolás D. Leclerc, Claude Maletto, Belkys Angélica Marinho, Fábio V. Molina, Guido Nicolas Molinari, Maria Paula Moron, Victor Gabriel Oliveira, Sergio C. Taboga, Oscar Alberto |
| author_facet | Molinari, Maria Paula Crespo, Maria Ines Molina, Guido Nicolas Dho, Nicolás D. Marinho, Fábio V. Maletto, Belkys Angélica Leclerc, Claude Oliveira, Sergio C. Taboga, Oscar Alberto Cebrian, Ignacio Moron, Victor Gabriel |
| author_sort | Molinari, Maria Paula |
| collection | INTA Digital |
| description | Although the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A novel strategy based on capsid display carrying foreign antigens in the AcMNPV particle further improved the immune response by eliciting CD8+ T cell activation. In this study, we analyze the intracellular mechanisms and signalling pathways involved in CD8+ T cell activation by capsid display. Our results show that baculovirus can attach to the cell surface, enter dendritic cells (DCs), transit within endocytic vesicles and escape to the cytosol for further degradation by the proteasome. We found that the availability of viral proteins, endosomal acidification, and proteasome activity are needed for efficient Major Histocompatibility Complex class-I presentation by baculovirus carrying Ovalbumin in the viral capsid. Importantly, we demonstrated with this strategy that the induction of cytotoxic T cells and IL-12 production by DCs are TLR9-dependent and STING-independent. Finally, our study shows differential intracellular processing for capsid and surface baculovirus proteins in DCs and highlights the role of different danger receptors during cytotoxic T cell priming through the capsid display delivery system, which could lead to improved baculovirus-based vaccines development. |
| format | info:ar-repo/semantics/artículo |
| id | INTA15190 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Wiley |
| publisherStr | Wiley |
| record_format | dspace |
| spelling | INTA151902023-09-13T10:37:04Z TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display Molinari, Maria Paula Crespo, Maria Ines Molina, Guido Nicolas Dho, Nicolás D. Marinho, Fábio V. Maletto, Belkys Angélica Leclerc, Claude Oliveira, Sergio C. Taboga, Oscar Alberto Cebrian, Ignacio Moron, Victor Gabriel Baculovirus Citotoxicidad Antígenos Autographa californica Cytotoxicity Antigens Capsid Display Visualización de la Cápside Although the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A novel strategy based on capsid display carrying foreign antigens in the AcMNPV particle further improved the immune response by eliciting CD8+ T cell activation. In this study, we analyze the intracellular mechanisms and signalling pathways involved in CD8+ T cell activation by capsid display. Our results show that baculovirus can attach to the cell surface, enter dendritic cells (DCs), transit within endocytic vesicles and escape to the cytosol for further degradation by the proteasome. We found that the availability of viral proteins, endosomal acidification, and proteasome activity are needed for efficient Major Histocompatibility Complex class-I presentation by baculovirus carrying Ovalbumin in the viral capsid. Importantly, we demonstrated with this strategy that the induction of cytotoxic T cells and IL-12 production by DCs are TLR9-dependent and STING-independent. Finally, our study shows differential intracellular processing for capsid and surface baculovirus proteins in DCs and highlights the role of different danger receptors during cytotoxic T cell priming through the capsid display delivery system, which could lead to improved baculovirus-based vaccines development. Instituto de Biotecnología Fil: Molinari, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Molinari, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Molinari, Maria Paula. Universidad Nacional de Moreno. Departamento de Ciencias Aplicadas y Tecnología (DCAyT); Argentina Fil: Crespo, Maria Ines. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina Fil: Crespo, Maria Ines. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI); Argentina Fil: Crespo, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Molina, Guido Nicolás. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina Fil: Molina, Guido Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Molina, Guido Nicolás. Universidad Nacional de Moreno. Departamento de Ciencias Aplicadas y Tecnología (DCAyT); Argentina Fil: Dho, Nicolás D. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina Fil: Dho, Nicolás D. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI); Argentina Fil: Dho, Nicolás D. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marinho, Fábio V. Federal University of Minas Gerais. Institute of Biological Sciences. Department of Biochemistry and Immunology; Brasil Fil: Maletto, Belkys Angélica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina Fil: Maletto, Belkys Angélica. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI); Argentina Fil: Maletto, Belkys Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Leclerc, Claude. Institut Pasteur. Departement d’Immunologie; Francia Fil: Oliveira, Sergio C. Federal University of Minas Gerais. Institute of Biological Sciences. Department of Biochemistry and Immunology; Brasil Fil: Oliveira, Sergio C. University of Sao Paulo. Institute of Biomedical Sciences. Department of Immunology; Brasil 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: Cebrian, Ignacio. Universidad Nacional de Cuyo. Instituto de Histología y Embriología de Mendoza (IHEM); Argentina Fil: Cebrian, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Moron, Victor Gabriel. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina Fil: Moron, Victor Gabriel. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI); Argentina Fil: Moron, Victor Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2023-09-13T10:30:09Z 2023-09-13T10:30:09Z 2023-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/15190 https://onlinelibrary.wiley.com/doi/10.1111/imm.13607 1365-2567 https://doi.org/10.1111/imm.13607 eng info:eu-repograntAgreement/INTA/2019-PD-E5-I102-001, Desarrollo de vacunas y tecnologías para mejorar las estrategias profilácticas y terapéuticas de las enfermedades que afectan la producción animal y la salud pública 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 Wiley Immunology 169 (1) : 27-41 (Mayo 2023) |
| spellingShingle | Baculovirus Citotoxicidad Antígenos Autographa californica Cytotoxicity Antigens Capsid Display Visualización de la Cápside Molinari, Maria Paula Crespo, Maria Ines Molina, Guido Nicolas Dho, Nicolás D. Marinho, Fábio V. Maletto, Belkys Angélica Leclerc, Claude Oliveira, Sergio C. Taboga, Oscar Alberto Cebrian, Ignacio Moron, Victor Gabriel TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| title | TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| title_full | TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| title_fullStr | TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| title_full_unstemmed | TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| title_short | TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| title_sort | tlr9 activation is required for cytotoxic response elicited by baculovirus capsid display |
| topic | Baculovirus Citotoxicidad Antígenos Autographa californica Cytotoxicity Antigens Capsid Display Visualización de la Cápside |
| url | http://hdl.handle.net/20.500.12123/15190 https://onlinelibrary.wiley.com/doi/10.1111/imm.13607 https://doi.org/10.1111/imm.13607 |
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