Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators
Dengue is an arboviral disease caused by dengue virus (DENV), which is transmitted to humans by <i>Aedes aegypti</i> mosquitoes. Infection by DENV most commonly results in a mild flu-like illness; however, the disease has been increasingly associated with neurological symptomatology. Thi...
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MDPI AG
2020-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/6/603 |
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| author | Natália Salomão Kíssila Rabelo Carlos Basílio-de-Oliveira Rodrigo Basílio-de-Oliveira Luiz Geraldo Flávia Lima Flávia dos Santos Gerard Nuovo Edson R. A. Oliveira Marciano Paes |
| author_facet | Natália Salomão Kíssila Rabelo Carlos Basílio-de-Oliveira Rodrigo Basílio-de-Oliveira Luiz Geraldo Flávia Lima Flávia dos Santos Gerard Nuovo Edson R. A. Oliveira Marciano Paes |
| author_sort | Natália Salomão |
| collection | DOAJ |
| description | Dengue is an arboviral disease caused by dengue virus (DENV), which is transmitted to humans by <i>Aedes aegypti</i> mosquitoes. Infection by DENV most commonly results in a mild flu-like illness; however, the disease has been increasingly associated with neurological symptomatology. This association draws attention to further investigations on the impact of DENV infection in the host’s central nervous system. Here, we analyzed brain samples of three fatal dengue cases that occurred in 2002 during an outbreak in Rio de Janeiro, Brazil. Brain tissues of these cases were marked by histopathological alterations, such as degenerated neurons, demyelination, hemorrhage, edema, and increased numbers of astrocytes and microglial cells. Samples were also characterized by lymphocytic infiltrates mainly composed of CD8 T cells. DENV replication was evidenced in neurons, microglia and endothelial cells through immunohistochemistry and in situ hybridization techniques. Pro-inflammatory cytokines, such as TNF-α and IFN-γ were detected in microglia, while endothelial cells were marked by the expression of RANTES/CCL5. Cytoplasmic HMGB1 and the production of nitric oxide were also found in neurons and microglial cells. This work highlights the possible participation of several local pro-inflammatory mediators in the establishment of dengue neuropathogenesis. |
| first_indexed | 2024-03-10T19:27:23Z |
| format | Article |
| id | doaj.art-119e2934e1be48c9b569bda056b80cca |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T19:27:23Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-119e2934e1be48c9b569bda056b80cca2023-11-20T02:23:04ZengMDPI AGViruses1999-49152020-05-0112660310.3390/v12060603Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory MediatorsNatália Salomão0Kíssila Rabelo1Carlos Basílio-de-Oliveira2Rodrigo Basílio-de-Oliveira3Luiz Geraldo4Flávia Lima5Flávia dos Santos6Gerard Nuovo7Edson R. A. Oliveira8Marciano Paes9Interdisciplinary Medical Research Laboratory Rio de Janeiro, Oswaldo Cruz Foundation, 21040-900 Rio de Janeiro, BrazilUltrastructure and Tissue Biology Laboratory Rio de Janeiro, Rio de Janeiro State University, 20551-030 Rio de Janeiro, BrazilPathological Anatomy, Gaffrée Guinle University Hospital Rio de Janeiro, Federal University of the State of Rio de Janeiro, 20270-004 Rio de Janeiro, BrazilPathological Anatomy, Gaffrée Guinle University Hospital Rio de Janeiro, Federal University of the State of Rio de Janeiro, 20270-004 Rio de Janeiro, BrazilGlial Cell Biology Laboratory, Institute of Biomedical Sciences Rio de Janeiro, Federal University of Rio de Janeiro, 21941-590 Rio de Janeiro, BrazilGlial Cell Biology Laboratory, Institute of Biomedical Sciences Rio de Janeiro, Federal University of Rio de Janeiro, 21941-590 Rio de Janeiro, BrazilViral Immunology Laboratory, Oswaldo Cruz Institute Rio de Janeiro, Oswaldo Cruz Foundation, 21040-900 Rio de Janeiro, BrazilOhio State University Comprehensive Cancer Center, Ohio State University Foundation, Columbus, OH 43210, USADepartment of Microbiology and Immunology Chicago, University of Illinois at Chicago, Chicago, IL 60612, USAInterdisciplinary Medical Research Laboratory Rio de Janeiro, Oswaldo Cruz Foundation, 21040-900 Rio de Janeiro, BrazilDengue is an arboviral disease caused by dengue virus (DENV), which is transmitted to humans by <i>Aedes aegypti</i> mosquitoes. Infection by DENV most commonly results in a mild flu-like illness; however, the disease has been increasingly associated with neurological symptomatology. This association draws attention to further investigations on the impact of DENV infection in the host’s central nervous system. Here, we analyzed brain samples of three fatal dengue cases that occurred in 2002 during an outbreak in Rio de Janeiro, Brazil. Brain tissues of these cases were marked by histopathological alterations, such as degenerated neurons, demyelination, hemorrhage, edema, and increased numbers of astrocytes and microglial cells. Samples were also characterized by lymphocytic infiltrates mainly composed of CD8 T cells. DENV replication was evidenced in neurons, microglia and endothelial cells through immunohistochemistry and in situ hybridization techniques. Pro-inflammatory cytokines, such as TNF-α and IFN-γ were detected in microglia, while endothelial cells were marked by the expression of RANTES/CCL5. Cytoplasmic HMGB1 and the production of nitric oxide were also found in neurons and microglial cells. This work highlights the possible participation of several local pro-inflammatory mediators in the establishment of dengue neuropathogenesis.https://www.mdpi.com/1999-4915/12/6/603denguehuman fatal casesneuropathogenesisinflammationcentral nervous system |
| spellingShingle | Natália Salomão Kíssila Rabelo Carlos Basílio-de-Oliveira Rodrigo Basílio-de-Oliveira Luiz Geraldo Flávia Lima Flávia dos Santos Gerard Nuovo Edson R. A. Oliveira Marciano Paes Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators Viruses dengue human fatal cases neuropathogenesis inflammation central nervous system |
| title | Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators |
| title_full | Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators |
| title_fullStr | Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators |
| title_full_unstemmed | Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators |
| title_short | Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators |
| title_sort | fatal dengue cases reveal brain injury and viral replication in brain resident cells associated with the local production of pro inflammatory mediators |
| topic | dengue human fatal cases neuropathogenesis inflammation central nervous system |
| url | https://www.mdpi.com/1999-4915/12/6/603 |
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