Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes
Abstract The vaccinia virus (VACV) is the most studied and well-characterised member of the Poxviridae family. However, the mechanisms through which it modulates redox homeostasis in host cells remain unclear. Although oxidative stress, which is marked by elevated levels of reactive species, contrib...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-14433-x |
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| author | Marília Bueno da Silva Menegatto Ariane Coelho Ferraz Rafaela Lameira Souza Lima Pedro Henrique Guimarães Oluwashola Samuel Ola-Olu Pedro Alves Machado-Junior Wellington Carvalho Malta Thaís de Fátima Silva Moraes Frank Silva Bezerra Breno de Mello Silva José Carlos de Magalhães Jordana Grazziela Alves Coelho dos Reis Flávio Guimarães da Fonseca Giliane de Souza Trindade Erna Geessien Kroon Cintia Lopes de Brito Magalhães |
| author_facet | Marília Bueno da Silva Menegatto Ariane Coelho Ferraz Rafaela Lameira Souza Lima Pedro Henrique Guimarães Oluwashola Samuel Ola-Olu Pedro Alves Machado-Junior Wellington Carvalho Malta Thaís de Fátima Silva Moraes Frank Silva Bezerra Breno de Mello Silva José Carlos de Magalhães Jordana Grazziela Alves Coelho dos Reis Flávio Guimarães da Fonseca Giliane de Souza Trindade Erna Geessien Kroon Cintia Lopes de Brito Magalhães |
| author_sort | Marília Bueno da Silva Menegatto |
| collection | DOAJ |
| description | Abstract The vaccinia virus (VACV) is the most studied and well-characterised member of the Poxviridae family. However, the mechanisms through which it modulates redox homeostasis in host cells remain unclear. Although oxidative stress, which is marked by elevated levels of reactive species, contributes to the pathogenesis of many viral infections, poxviruses may adopt distinct strategies. VACV has redox effector proteins that are released into the cytosol when the virus penetrates the host cell. This study demonstrates for the first time that VACV infection leads to the activation of the nuclear factor erythroid 2 (Nrf2)/antioxidant response element pathway, a key regulator of cellular antioxidant responses, a mechanism not previously described for any poxvirus. Using BSC-40 cells, we observed that VACV significantly reduced reactive oxygen and nitrogen species levels, downregulated inducible nitric oxide synthase, and enhanced the activity of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. This antioxidant shift is correlated with increased Nrf2 activity and the upregulation of its downstream targets. This virus-induced antioxidant state may be an immunomodulatory mechanism that facilitates viral replication by dampening host defence. Thus, our findings expand the current understanding of virus–host interactions in poxvirus infections. |
| format | Article |
| id | doaj-art-429810cd9f55443fad3d33873f408cbe |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-429810cd9f55443fad3d33873f408cbe2025-08-20T03:42:53ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-14433-xVaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymesMarília Bueno da Silva Menegatto0Ariane Coelho Ferraz1Rafaela Lameira Souza Lima2Pedro Henrique Guimarães3Oluwashola Samuel Ola-Olu4Pedro Alves Machado-Junior5Wellington Carvalho Malta6Thaís de Fátima Silva Moraes7Frank Silva Bezerra8Breno de Mello Silva9José Carlos de Magalhães10Jordana Grazziela Alves Coelho dos Reis11Flávio Guimarães da Fonseca12Giliane de Souza Trindade13Erna Geessien Kroon14Cintia Lopes de Brito Magalhães15Programa de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Biotecnologia, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Biotecnologia, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Microbiologia, Universidade Federal de Minas GeraisPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoPrograma de Pós Graduação em Biotecnologia, Universidade Federal de São João del-ReiPrograma de Pós Graduação em Microbiologia, Universidade Federal de Minas GeraisPrograma de Pós Graduação em Microbiologia, Universidade Federal de Minas GeraisPrograma de Pós Graduação em Microbiologia, Universidade Federal de Minas GeraisPrograma de Pós Graduação em Microbiologia, Universidade Federal de Minas GeraisPrograma de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro PretoAbstract The vaccinia virus (VACV) is the most studied and well-characterised member of the Poxviridae family. However, the mechanisms through which it modulates redox homeostasis in host cells remain unclear. Although oxidative stress, which is marked by elevated levels of reactive species, contributes to the pathogenesis of many viral infections, poxviruses may adopt distinct strategies. VACV has redox effector proteins that are released into the cytosol when the virus penetrates the host cell. This study demonstrates for the first time that VACV infection leads to the activation of the nuclear factor erythroid 2 (Nrf2)/antioxidant response element pathway, a key regulator of cellular antioxidant responses, a mechanism not previously described for any poxvirus. Using BSC-40 cells, we observed that VACV significantly reduced reactive oxygen and nitrogen species levels, downregulated inducible nitric oxide synthase, and enhanced the activity of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. This antioxidant shift is correlated with increased Nrf2 activity and the upregulation of its downstream targets. This virus-induced antioxidant state may be an immunomodulatory mechanism that facilitates viral replication by dampening host defence. Thus, our findings expand the current understanding of virus–host interactions in poxvirus infections.https://doi.org/10.1038/s41598-025-14433-xVaccinia virusPoxvirusesAntioxidantRedox homeostasis |
| spellingShingle | Marília Bueno da Silva Menegatto Ariane Coelho Ferraz Rafaela Lameira Souza Lima Pedro Henrique Guimarães Oluwashola Samuel Ola-Olu Pedro Alves Machado-Junior Wellington Carvalho Malta Thaís de Fátima Silva Moraes Frank Silva Bezerra Breno de Mello Silva José Carlos de Magalhães Jordana Grazziela Alves Coelho dos Reis Flávio Guimarães da Fonseca Giliane de Souza Trindade Erna Geessien Kroon Cintia Lopes de Brito Magalhães Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes Scientific Reports Vaccinia virus Poxviruses Antioxidant Redox homeostasis |
| title | Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes |
| title_full | Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes |
| title_fullStr | Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes |
| title_full_unstemmed | Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes |
| title_short | Vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes |
| title_sort | vaccinia virus modulates the redox environment by inhibiting reactive oxygen and nitrogen species with increased activity of endogenous antioxidant enzymes |
| topic | Vaccinia virus Poxviruses Antioxidant Redox homeostasis |
| url | https://doi.org/10.1038/s41598-025-14433-x |
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