Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response

Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivat...

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Autores principales:	Glaucia M. Almeida, Juliano P. Souza, Niele D. Mendes, Marjorie C. Pontelli, Nathalia R. Pinheiro, Giovanna O. Nogueira, Ricardo S. Cardoso, Isadora M. Paiva, Gustavo D. Ferrari, Flávio P. Veras, Fernando Q. Cunha, Jose A. C. Horta-Junior, Luciane C. Alberici, Thiago M. Cunha, Guilherme G. Podolsky-Gondim, Luciano Neder, Eurico Arruda, Adriano Sebollela
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	arboviruses viral encephalitis histocultures neuroinflammation neuroinfection neurotropic virus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/9906ed265b86407d84abf4ac068b9fc7
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spelling	oai:doaj.org-article:9906ed265b86407d84abf4ac068b9fc72021-11-30T12:32:56ZNeural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response1662-453X10.3389/fnins.2021.674576https://doaj.org/article/9906ed265b86407d84abf4ac068b9fc72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.674576/fullhttps://doaj.org/toc/1662-453XOropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.Glaucia M. AlmeidaGlaucia M. AlmeidaJuliano P. SouzaJuliano P. SouzaNiele D. MendesNiele D. MendesMarjorie C. PontelliMarjorie C. PontelliNathalia R. PinheiroGiovanna O. NogueiraRicardo S. CardosoRicardo S. CardosoIsadora M. PaivaIsadora M. PaivaGustavo D. FerrariFlávio P. VerasFlávio P. VerasFernando Q. CunhaFernando Q. CunhaJose A. C. Horta-JuniorLuciane C. AlbericiThiago M. CunhaThiago M. CunhaGuilherme G. Podolsky-GondimLuciano NederEurico ArrudaEurico ArrudaAdriano SebollelaFrontiers Media S.A.articlearbovirusesviral encephalitishistoculturesneuroinflammationneuroinfectionneurotropic virusNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	arboviruses viral encephalitis histocultures neuroinflammation neuroinfection neurotropic virus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	arboviruses viral encephalitis histocultures neuroinflammation neuroinfection neurotropic virus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Glaucia M. Almeida Glaucia M. Almeida Juliano P. Souza Juliano P. Souza Niele D. Mendes Niele D. Mendes Marjorie C. Pontelli Marjorie C. Pontelli Nathalia R. Pinheiro Giovanna O. Nogueira Ricardo S. Cardoso Ricardo S. Cardoso Isadora M. Paiva Isadora M. Paiva Gustavo D. Ferrari Flávio P. Veras Flávio P. Veras Fernando Q. Cunha Fernando Q. Cunha Jose A. C. Horta-Junior Luciane C. Alberici Thiago M. Cunha Thiago M. Cunha Guilherme G. Podolsky-Gondim Luciano Neder Eurico Arruda Eurico Arruda Adriano Sebollela Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
description	Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.
format	article
author	Glaucia M. Almeida Glaucia M. Almeida Juliano P. Souza Juliano P. Souza Niele D. Mendes Niele D. Mendes Marjorie C. Pontelli Marjorie C. Pontelli Nathalia R. Pinheiro Giovanna O. Nogueira Ricardo S. Cardoso Ricardo S. Cardoso Isadora M. Paiva Isadora M. Paiva Gustavo D. Ferrari Flávio P. Veras Flávio P. Veras Fernando Q. Cunha Fernando Q. Cunha Jose A. C. Horta-Junior Luciane C. Alberici Thiago M. Cunha Thiago M. Cunha Guilherme G. Podolsky-Gondim Luciano Neder Eurico Arruda Eurico Arruda Adriano Sebollela
author_facet	Glaucia M. Almeida Glaucia M. Almeida Juliano P. Souza Juliano P. Souza Niele D. Mendes Niele D. Mendes Marjorie C. Pontelli Marjorie C. Pontelli Nathalia R. Pinheiro Giovanna O. Nogueira Ricardo S. Cardoso Ricardo S. Cardoso Isadora M. Paiva Isadora M. Paiva Gustavo D. Ferrari Flávio P. Veras Flávio P. Veras Fernando Q. Cunha Fernando Q. Cunha Jose A. C. Horta-Junior Luciane C. Alberici Thiago M. Cunha Thiago M. Cunha Guilherme G. Podolsky-Gondim Luciano Neder Eurico Arruda Eurico Arruda Adriano Sebollela
author_sort	Glaucia M. Almeida
title	Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
title_short	Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
title_full	Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
title_fullStr	Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
title_full_unstemmed	Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
title_sort	neural infection by oropouche virus in adult human brain slices induces an inflammatory and toxic response
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9906ed265b86407d84abf4ac068b9fc7
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Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response

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