Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease
cGAMP-specific nucleases (poxins) are a recently described family of proteins dedicated to obstructing cyclic GMP-AMP synthase signaling (cGAS), an important sensor triggered by cytoplasmic viral replication that activates type I interferon (IFN) production. The B2R gene of vaccinia viruses (VACV) c...
| Autores: | ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artigo |
| Estado: | Published version |
| Data de publicação: | 2023 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/202057 |
| Acesso em linha: | https://hdl.handle.net/2445/202057 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | Immunitat Animals Interferó Nucleòtids Immunity Interferon Nucleotides |
| _version_ | 1878732006418808832 |
|---|---|
| author | Riederer, Stephanie |
| author2 | Canizo, Ana del Navas, Javier Peter, Marlowe G. Link, Ellen K. Sutter, Gerd Rojas, Juan José |
| author2_role | author author author author author author |
| author_browse | Canizo, Ana del Link, Ellen K. Navas, Javier Peter, Marlowe G. Riederer, Stephanie Rojas, Juan José Sutter, Gerd |
| author_facet | Riederer, Stephanie Canizo, Ana del Navas, Javier Peter, Marlowe G. Link, Ellen K. Sutter, Gerd Rojas, Juan José |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | cGAMP-specific nucleases (poxins) are a recently described family of proteins dedicated to obstructing cyclic GMP-AMP synthase signaling (cGAS), an important sensor triggered by cytoplasmic viral replication that activates type I interferon (IFN) production. The B2R gene of vaccinia viruses (VACV) codes for one of these nucleases. Here, we evaluated the effects of inactivating the VACV B2 nuclease in the context of an oncolytic VACV. VACV are widely used as anti-cancer vectors due to their capacity to activate immune responses directed against tumor antigens. We aimed to elicit robust antitumor immunity by preventing viral inactivation of the cGAS/STING/IRF3 pathway after infection of cancer cells. Activation of such a pathway is associated with a dominant T helper 1 (Th1) cell differentiation of the response, which benefits antitumor outcomes. Deletion of the B2R gene resulted in enhanced IRF3 phosphorylation and type I IFN expression after infection of tumor cells, while effective VACV replication remained unimpaired, both in vitro and in vivo. In syngeneic mouse tumor models, the absence of the VACV cGAMP-specific nuclease translated into improved antitumor activity, which was associated with antitumor immunity directed against tumor epitopes. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_3b0519888a9b5d9447d359d6c065eb2e |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/202057 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | Springer Nature |
| publisherStr | Springer Nature |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease Riederer, Stephanie Canizo, Ana del Navas, Javier Peter, Marlowe G. Link, Ellen K. Sutter, Gerd Rojas, Juan José Immunitat Animals Interferó Nucleòtids Immunity Interferon Nucleotides cGAMP-specific nucleases (poxins) are a recently described family of proteins dedicated to obstructing cyclic GMP-AMP synthase signaling (cGAS), an important sensor triggered by cytoplasmic viral replication that activates type I interferon (IFN) production. The B2R gene of vaccinia viruses (VACV) codes for one of these nucleases. Here, we evaluated the effects of inactivating the VACV B2 nuclease in the context of an oncolytic VACV. VACV are widely used as anti-cancer vectors due to their capacity to activate immune responses directed against tumor antigens. We aimed to elicit robust antitumor immunity by preventing viral inactivation of the cGAS/STING/IRF3 pathway after infection of cancer cells. Activation of such a pathway is associated with a dominant T helper 1 (Th1) cell differentiation of the response, which benefits antitumor outcomes. Deletion of the B2R gene resulted in enhanced IRF3 phosphorylation and type I IFN expression after infection of tumor cells, while effective VACV replication remained unimpaired, both in vitro and in vivo. In syngeneic mouse tumor models, the absence of the VACV cGAMP-specific nuclease translated into improved antitumor activity, which was associated with antitumor immunity directed against tumor epitopes. Springer Nature https://hdl.handle.net/2445/202057 |
| spellingShingle | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease Riederer, Stephanie Immunitat Animals Interferó Nucleòtids Immunity Interferon Nucleotides |
| status_str | publishedVersion |
| title | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease |
| title_full | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease |
| title_fullStr | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease |
| title_full_unstemmed | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease |
| title_short | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease |
| title_sort | Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease |
| topic | Immunitat Animals Interferó Nucleòtids Immunity Interferon Nucleotides |
| topic_facet | Immunitat Animals Interferó Nucleòtids Immunity Interferon Nucleotides |
| url | https://hdl.handle.net/2445/202057 |