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The role of IRF-5 in Oropouche virus pathogenesis and neurovirulence

Grant number: 17/26908-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2018
Effective date (End): April 30, 2022
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator: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

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)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VENCESLAU, EMANUELLA MENESES; SIQUEIRA GUIDA, JOSE PAULO; NOBREGA, GUILHERME DE MORAES; SAMOGIM, ANA PAULA; PARISE, PIERINA LORENCINI; JAPECANGA, RODOLFO ROSA; DE TOLEDO-TEIXEIRA, DANIEL AUGUSTO; FORATO, JULIA; ANTOLINI-TAVARES, ARTHUR; SOUZA, ARETHUSA; ALTEMANI, ALBINA; CONSONNI, SILVIO ROBERTO; PASSINI, RENATO; AMARAL, ELIANA; PROENCA-MODENA, JOSE LUIZ; COSTA, MARIA LAURA; NETWORK, ZIKA-UNICAMP. Adequate Placental Sampling for the Diagnosis and Characterization of Placental Infection by Zika Virus. FRONTIERS IN MICROBIOLOGY, v. 11, FEB 21 2020. Web of Science Citations: 0.

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