| Grant number: | 17/26908-0 |
| Support type: | Scholarships in Brazil - Doctorate (Direct) |
| Effective date (Start): | May 01, 2018 |
| Effective date (End): | April 30, 2023 |
| Field of knowledge: | Biological Sciences - Microbiology - Biology and Physiology of Microorganisms |
| Principal researcher: | José Luiz Proença Módena |
| Grantee: | Pierina Lorencini Parise |
| Home Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated research grant: | 16/00194-8 - Pathogenesis and neurovirulence of emerging viruses in Brazil, AP.JP |
| Associated scholarship(s): | 22/04420-3 - Role of IRF5 in Oropouche vírus pathogenesis and neurovirulence, BE.EP.DD |
Abstract The Oropouche Vírus (OROV) is an emergent arbovirus transmitted by the bite of Culicoides paraensis, a hematophagous fly that circulates in the North and Northeast of Brazil. Like other arboviruses, including Zika and Chikungunya, OROV causes an exanthematic febrile illness associated with neurological complications in some of the infected patients. Although OROV has been shown to cross the blood-brain barrier and cause infection in the Central Nervous System (CNS) of neonatal mice and hamsters, little is known about the pathogenetic mechanisms associated with the breakdown of this barrier. Recently, our group demonstrated that IRF-5, a transcription factor activated after recognition of PAMPs (Pathogen-Associated Molecular Patterns) conserved pathogen structures, is essential in the control of neuroinvasion by OROV. Thus, the objective of this project is to characterize how IRF-5 controls the neuroinvasion by OROV. For this, we characterize OROV infection and the expression of total RNAs by RNAseq in PBMCs (polymorphonuclear cells) and primary cultures of cerebral endothelium of wild animals and knockouts for IRF5. In addition, we will examine the integrity of the endothelial barrier in transwell experiments with established lineages and primary cultures of endothelial cells, by measuring Transendothelial Electrical Resistance (TEER), the amount of virus that crossed the monolayer, and the integrity of the occlusive junctions by confocal microscopy. Such experiments will be conducted in the presence and absence of vírus and the supernatant of artificially infected PBMCs. Finally, we will analyze viral mortality and tropism in animals that do not express IRF-5 in macrophages, dendritic cells and endothelium, using the Cre/LoxP recombination system. (AU) | |
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