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Evaluation of inflammation of human villous trophoblasts in Zika and dengue virus

Grant number: 16/24680-9
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2017
Effective date (End): November 30, 2018
Field of knowledge:Biological Sciences - Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Maria Notomi Sato
Grantee:Anna Cláudia Calvielli Castelo Branco
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Zika virus (ZKV) belongs to the flaviviridae family which includes speciesTransmitted mainly by Aedes sp. In Brazil, cases ofFetal microcephaly were associated with ZKV infection. SeveralTolerance during gestation and in the antiviral response and / orAnti-inflammatory drugs are indispensable for the understanding of theCongenital disease of the ZKV. Inflammation of placental cells, such as trophoblastsMay be associated with increased infections and higherPreterm births. In addition, neural inflammation induced byToll-like receptors (TLRs) is able to facilitate viral infection and contribute to theDevelopment of neurodegenerative diseases. In this way, it is possible thatThe inflammation induced by TLR4 in villous trophoblasts favors infection byZKV. For this, the inflammation of lineage of villous trophoblastsAnd primary villous trophoblasts through the TLR4 agonist (LPS) andSubsequently infected with ZKV and compared with another flavivirus, dengue(DENV). Viral replication, cytokine production and chemokines will be evaluated.Inflammatory, regulatory and antiviral agents, and expression of inflammatory receptorsAnd antiviral drugs. Subsequently, for the study of signaling pathways that lead toInflammatory drugs, some anti-inflammatory drugs will be tested andViral replication, such as the inhibitor of IKK-2, TLR4 antagonist (LPS-RS),Resveratrol, a natural agent with antioxidant and anti-inflammatory action and AcYVAD-cmk,An inhibitor of caspase-1, which acts to inhibit the final step of theInflammomas. After drug selection, the signaling pathway will be analyzed,Through pharmacological antagonism and pathway phosphorylation. The developmentOf the project may elucidate the role of inflammation during congenital infectionBy ZKV and to point out immunomodulatory strategies for the treatment of infection. (AU)

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