دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response.
المؤلفون: Almeida GM; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Souza JP; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Mendes ND; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pontelli MC; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pinheiro NR; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Nogueira GO; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Cardoso RS; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Paiva IM; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Ferrari GD; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Veras FP; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Cunha FQ; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Horta-Junior JAC; Department of Structural and Functional Biology (Anatomy), Institute of Biosciences, São Paulo State University, Botucatu, Brazil., Alberici LC; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Cunha TM; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Podolsky-Gondim GG; Division of Neurosurgery, Department of Surgery and Anatomy, Ribeirão Preto Clinics Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Neder L; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Arruda E; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Sebollela A; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
المصدر: Frontiers in neuroscience [Front Neurosci] 2021 Nov 23; Vol. 15, pp. 674576. Date of Electronic Publication: 2021 Nov 23 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101478481 Publication Model: eCollection Cited Medium: Print ISSN: 1662-4548 (Print) Linking ISSN: 1662453X NLM ISO Abbreviation: Front Neurosci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Almeida, Souza, Mendes, Pontelli, Pinheiro, Nogueira, Cardoso, Paiva, Ferrari, Veras, Cunha, Horta-Junior, Alberici, Cunha, Podolsky-Gondim, Neder, Arruda and Sebollela.)
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فهرسة مساهمة: Keywords: arboviruses; histocultures; human brain; neuroinfection; neuroinflammation; neurotropic virus; viral encephalitis
تواريخ الأحداث: Date Created: 20211210 Latest Revision: 20230921
رمز التحديث: 20230921
مُعرف محوري في PubMed: PMC8651276
DOI: 10.3389/fnins.2021.674576
PMID: 34887719
قاعدة البيانات: MEDLINE
الوصف
تدمد:1662-4548
DOI:10.3389/fnins.2021.674576