Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2013 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/59316 |
Resumo: | Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil |
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Souza, Katia Paulino Ribeiro deSilva, Emanuele GuimarãesRocha, Eliseu Soares de OliveiraFigueiredo, Leandra BarcelosAlmeida-Leite, Camila Megale deArantes, Rosa Maria EstevesGomes, Juliana de Assis SilvaFerreira, Gustavo PortelaOliveira, Jaquelline Germano deKroon, Erna GeessienCampos, Marco Antônio2023-06-30T17:32:00Z2023-06-30T17:32:00Z2013SOUZA, Kátia Paulino Ribeiro de et al. Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement. Virol J.; v. 10, 267, 2013. doi: 10.1186/1743-422X-10-2671743-422Xhttps://www.arca.fiocruz.br/handle/icict/5931610.1186/1743-422X-10-267engBioMed CentralNitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvementinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUniversidade Federal do Piauí. Parnaíba, PI, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilBackground: The clinical presentation of dengue is classified by the World Health Organization into dengue without warning signs, dengue with warning signs and severe dengue. Reports of neurological disease caused by Dengue virus (DENV) are becoming frequent, with symptoms that include reduced consciousness, severe headache, neck stiffness, focal neurological signs, tense fontanelle and convulsions. However, the immune mechanisms involved in neurovirulence remain poorly understood. Here we present a mouse model in which one genotype of DENV is inoculated by the intracranial route and infects C57/BL6 mice and replicates in the brain, causing death of mice. Methods: Mice were infected with different serotypes/genotypes of DENV by the intracranial route to evaluate viral replication, host cytokine and nitric oxide synthase 2 (Nos2) expression in the brain via real-time PCR. Histological analysis of the brain tissues was also performed. An analysis of which cells were responsible for the expression of cytokines and Nos2 was performed using flow cytometry. Survival curves of infected animals were also generated. Results: DENV 3 genotype I infected mice and replicated in the brain, causing death in our murine model. The increased levels of NOS2 could be the cause of the death of infected mice, as viral replication correlates with increased Nos2 and cytokine expression in the brain of C57BL/6 mice. In Nos2(-/-) mice that were infected with DENV, no clinical signs of infection were observed and cytokines were expressed at low levels, with the exception of interferon gamma (Ifng). Additionally, the Ifng(-/-) mice infected with DENV exhibited a severe and lethal disease, similar to the disease observed in C57BL/6 mice, while the DENV-infected Nos2(-/-) mice did not display increased mortality. Analyses of the brains from infected C57BL/6 mice revealed neuronal degeneration and necrosis during histopathologic examination. IFNg and NOS2 were produced in the brains of infected mice by CD4(+) T cells and macrophages, respectively. Conclusion: The neurovirulence of DENV 3 genotype I is associated with a deleterious role of NOS2 in the brain, confirming this murine model as an appropriate tool to study DENV neurovirulenceDengue virusMurine modelNeurovirulenceNeuropathogenesisImmunopathogenesisEncephalitisNitric oxide synthase 2Nitric oxideInterferon gammainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALNitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement.pdfNitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement.pdfapplication/pdf903494https://www.arca.fiocruz.br/bitstream/icict/59316/2/Nitric%20oxide%20synthase%20expression%20correlates%20with%20death%20in%20an%20experimental%20mouse%20model%20of%20dengue%20with%20CNS%20involvement.pdf97dee307d13b3408921b97a8d35b67c2MD52LICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/59316/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51icict/593162023-06-30 14:32:01.312oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-06-30T17:32:01Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| title |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| spellingShingle |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement Souza, Katia Paulino Ribeiro de Dengue virus Murine model Neurovirulence Neuropathogenesis Immunopathogenesis Encephalitis Nitric oxide synthase 2 Nitric oxide Interferon gamma |
| title_short |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| title_full |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| title_fullStr |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| title_full_unstemmed |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| title_sort |
Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement |
| author |
Souza, Katia Paulino Ribeiro de |
| author_facet |
Souza, Katia Paulino Ribeiro de Silva, Emanuele Guimarães Rocha, Eliseu Soares de Oliveira Figueiredo, Leandra Barcelos Almeida-Leite, Camila Megale de Arantes, Rosa Maria Esteves Gomes, Juliana de Assis Silva Ferreira, Gustavo Portela Oliveira, Jaquelline Germano de Kroon, Erna Geessien Campos, Marco Antônio |
| author_role |
author |
| author2 |
Silva, Emanuele Guimarães Rocha, Eliseu Soares de Oliveira Figueiredo, Leandra Barcelos Almeida-Leite, Camila Megale de Arantes, Rosa Maria Esteves Gomes, Juliana de Assis Silva Ferreira, Gustavo Portela Oliveira, Jaquelline Germano de Kroon, Erna Geessien Campos, Marco Antônio |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Souza, Katia Paulino Ribeiro de Silva, Emanuele Guimarães Rocha, Eliseu Soares de Oliveira Figueiredo, Leandra Barcelos Almeida-Leite, Camila Megale de Arantes, Rosa Maria Esteves Gomes, Juliana de Assis Silva Ferreira, Gustavo Portela Oliveira, Jaquelline Germano de Kroon, Erna Geessien Campos, Marco Antônio |
| dc.subject.en.en_US.fl_str_mv |
Dengue virus Murine model Neurovirulence Neuropathogenesis Immunopathogenesis Encephalitis Nitric oxide synthase 2 Nitric oxide Interferon gamma |
| topic |
Dengue virus Murine model Neurovirulence Neuropathogenesis Immunopathogenesis Encephalitis Nitric oxide synthase 2 Nitric oxide Interferon gamma |
| description |
Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil |
| publishDate |
2013 |
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2013 |
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2023-06-30T17:32:00Z |
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2023-06-30T17:32:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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SOUZA, Kátia Paulino Ribeiro de et al. Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement. Virol J.; v. 10, 267, 2013. doi: 10.1186/1743-422X-10-267 |
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https://www.arca.fiocruz.br/handle/icict/59316 |
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1743-422X |
| dc.identifier.doi.none.fl_str_mv |
10.1186/1743-422X-10-267 |
| identifier_str_mv |
SOUZA, Kátia Paulino Ribeiro de et al. Nitric oxide synthase expression correlates with death in an experimental mouse model of dengue with CNS involvement. Virol J.; v. 10, 267, 2013. doi: 10.1186/1743-422X-10-267 1743-422X 10.1186/1743-422X-10-267 |
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https://www.arca.fiocruz.br/handle/icict/59316 |
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BioMed Central |
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BioMed Central |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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