Study of central nervous system infection by the Oropouche vírus in adult human brain slice cultures

Author(s)

Glaucia Maria de Almeida

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-06-03

Examining board members

Adriano Silva Sebollela; Thiago Mattar Cunha; José Luiz Proença Modena

• Advisor: Adriano Silva Sebollela; Eurico de Arruda Neto

Abstract

The Oropouche virus (OROV), of the family Peribunyaviridae, genus Orthobunyavirus, is a causative agent of arbovirus called \"Oropouche fever\". This virus has the significant spreading capacity, and in recent years has been found in nonendemic region, especially in South American countries, including Brazil. Although some clinical evidences in alterations in central nervous system, as meningitis, has been associated with OROV infection, few studies involving OROV neuropathogenesis have been studied, and all knowledge obtained were showed from neonatal murine models. This difficulty in studying OROV neuropathogenesis in the human central nervous system is related to the lack of models that maintain the complexity of human brain. Therefore, in this study, we evaluated the OROV neuroinfection using adult human brain slices cultures. We showed for the first time that OROV infects human neural cells and caused tissue damage within 48 h post infection, such as loss of cell viability and TNF-α release, a proinflammatory cytokine. We showed, by immunofluorescence, microglia cells were the cell most susceptible to OROV infection, but that it retains the ability to infect neurons. This is the first study to report OROV infection in adult human brain model and should become useful in neuropathogenesis studies related to this emerging pathogen. (AU)

• FAPESP's process: 18/06614-4 - Determination of neuronal function and oxidative metabolic profile in free-floating adult human brain-derived slice cultures
• Grantee: Glaucia Maria de Almeida
• Support Opportunities: Scholarships in Brazil - Master