Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates

Detalhes bibliográficos
Autor(a) principal: Oliveira, Marina da Silva
Data de Publicação: 2023
Outros Autores: Cassiano, Larissa Marcely Gomes, Pioline, Jeanne, Carvalho, Ketyllen Reis Andrade de, Salim, Anna Christina de Matos, Alves, Pedro Augusto, Fernandes, Gabriel da Rocha, Machado, Alexandre de Magalhães Vieira, Coimbra, Roney Santos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/59622
Resumo: Fundação Oswaldo Cruz. Instituto René Rachou. Neurogenômica, Imunopatologia. Belo Horizonte, MG, Brazil.
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spelling Oliveira, Marina da SilvaCassiano, Larissa Marcely GomesPioline, JeanneCarvalho, Ketyllen Reis Andrade deSalim, Anna Christina de MatosAlves, Pedro AugustoFernandes, Gabriel da RochaMachado, Alexandre de Magalhães VieiraCoimbra, Roney Santos2023-07-17T19:44:23Z2023-07-17T19:44:23Z2023OLIVEIRA, Marina da Silva et al. Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates. J Neuroinflammation, v. 20, n. 1, p. 140-140, 2023. doi: 10.1186/s12974-023-02826-6.1742-2094https://www.arca.fiocruz.br/handle/icict/59622engBioMed CentralOrganotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolatesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto René Rachou. Neurogenômica, Imunopatologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Neurogenômica, Imunopatologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Neurogenômica, Imunopatologia. Belo Horizonte, MG, Brazil/Aix-Marseille University. Marseille, France.Fundação Oswaldo Cruz Instituto René Rachou. Imunologia de Doenças Virais. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Plataforma de Sequenciamento NGS. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz Instituto René Rachou. Imunologia de Doenças Virais. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Plataforma de Bioinformática. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz Instituto René Rachou. Imunologia de Doenças Virais. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Neurogenômica, Imunopatologia. Belo Horizonte, MG, Brazil.Introduction: Zika virus (ZIKV) caused an outbreak in Brazil, in 2015, being associated to microcephaly. ZIKV has a strong neurotropism leading to death of infected cells in different brain regions, including the hippocampus, a major site for neurogenesis. The neuronal populations of the brain are affected differently by ZIKV from Asian and African ancestral lineages. However, it remains to be investigated whether subtle variations in the ZIKV genome can impact hippocampus infection dynamics and host response. Objective: This study evaluated how two Brazilian ZIKV isolates, PE243 and SPH2015, that differ in two specific missense amino acid substitutions, one in the NS1 protein and the other in the NS4A protein, affect the hippocampal phenotype and transcriptome. Methods: Organotypic hippocampal cultures (OHC) from infant Wistar rats were infected with PE243 or SPH2015 and analyzed in time series using immunofluorescence, confocal microscopy, RNA-Seq and RT-qPCR. Results: Unique patterns of infection and changes in neuronal density in the OHC were observed for PE243 and SPH2015 between 8 and 48 h post infection (p.i.). Phenotypic analysis of microglia indicated that SPH2015 has a greater capacity for immune evasion. Transcriptome analysis of OHC at 16 h p.i. disclosed 32 and 113 differentially expressed genes (DEGs) in response to infection with PE243 and SPH2015, respectively. Functional enrichment analysis suggested that infection with SPH2015 activates mostly astrocytes rather than microglia. PE243 downregulated biological process of proliferation of brain cells and upregulated those associated with neuron death, while SPH2015 downregulated processes related to neuronal development. Both isolates downregulated cognitive and behavioral development processes. Ten genes were similarly regulated by both isolates. They are putative biomarkers of early hippocampus response to ZIKV infection. At 5, 7, and 10 days p.i., neuronal density of infected OHC remained below controls, and mature neurons of infected OHC showed an increase in the epigenetic mark H3K4me3, which is associated to a transcriptionally active state. This feature is more prominent in response to SPH2015. Conclusion: Subtle genetic diversity of the ZIKV affects the dynamics of viral dissemination in the hippocampus and host response in the early stages of infection, which may lead to different long-term effects in neuronal population.Chromatin remodelingNeurodegenerationNeuroinflammationOrganotypic hippocampal cultureTranscriptomeZika virusinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/59622/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALOrganotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates.pdfOrganotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates.pdfapplication/pdf4424641https://www.arca.fiocruz.br/bitstream/icict/59622/2/Organotypic%20hippocampal%20culture%20model%20reveals%20differential%20responses%20to%20highly%20similar%20Zika%20virus%20isolates.pdf373f9db6688a363699c6e16f5423ff6aMD52icict/596222023-07-17 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dc.title.en_US.fl_str_mv Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
title Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
spellingShingle Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
Oliveira, Marina da Silva
Chromatin remodeling
Neurodegeneration
Neuroinflammation
Organotypic hippocampal culture
Transcriptome
Zika virus
title_short Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
title_full Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
title_fullStr Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
title_full_unstemmed Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
title_sort Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates
author Oliveira, Marina da Silva
author_facet Oliveira, Marina da Silva
Cassiano, Larissa Marcely Gomes
Pioline, Jeanne
Carvalho, Ketyllen Reis Andrade de
Salim, Anna Christina de Matos
Alves, Pedro Augusto
Fernandes, Gabriel da Rocha
Machado, Alexandre de Magalhães Vieira
Coimbra, Roney Santos
author_role author
author2 Cassiano, Larissa Marcely Gomes
Pioline, Jeanne
Carvalho, Ketyllen Reis Andrade de
Salim, Anna Christina de Matos
Alves, Pedro Augusto
Fernandes, Gabriel da Rocha
Machado, Alexandre de Magalhães Vieira
Coimbra, Roney Santos
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Marina da Silva
Cassiano, Larissa Marcely Gomes
Pioline, Jeanne
Carvalho, Ketyllen Reis Andrade de
Salim, Anna Christina de Matos
Alves, Pedro Augusto
Fernandes, Gabriel da Rocha
Machado, Alexandre de Magalhães Vieira
Coimbra, Roney Santos
dc.subject.en.en_US.fl_str_mv Chromatin remodeling
Neurodegeneration
Neuroinflammation
Organotypic hippocampal culture
Transcriptome
Zika virus
topic Chromatin remodeling
Neurodegeneration
Neuroinflammation
Organotypic hippocampal culture
Transcriptome
Zika virus
description Fundação Oswaldo Cruz. Instituto René Rachou. Neurogenômica, Imunopatologia. Belo Horizonte, MG, Brazil.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-07-17T19:44:23Z
dc.date.available.fl_str_mv 2023-07-17T19:44:23Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv OLIVEIRA, Marina da Silva et al. Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates. J Neuroinflammation, v. 20, n. 1, p. 140-140, 2023. doi: 10.1186/s12974-023-02826-6.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/59622
dc.identifier.issn.en_US.fl_str_mv 1742-2094
identifier_str_mv OLIVEIRA, Marina da Silva et al. Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates. J Neuroinflammation, v. 20, n. 1, p. 140-140, 2023. doi: 10.1186/s12974-023-02826-6.
1742-2094
url https://www.arca.fiocruz.br/handle/icict/59622
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/59622/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/59622/2/Organotypic%20hippocampal%20culture%20model%20reveals%20differential%20responses%20to%20highly%20similar%20Zika%20virus%20isolates.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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