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Proteomic characterization of exosomes and their inflammatory miRNAs from extravillous trophoblast cells infected in vitro by Zika Virus

Grant number: 16/10522-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2016
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Maria Notomi Sato
Grantee:Luanda Mara da Silva Oliveira
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The infection caused by Zika virus (ZKV) has become a major public health issue in Brazil since 2014 and the association between ZKV infection during pregnancy and microcephaly has been broadly discussed. During pregnancy there is a balance between the fetal tolerance mechanisms, the mechanisms that regulate systemic inflammation and placental tissue generated in the presence of viral infection are essential to influence the impairment of fetal development. Placental trophoblasts release microvesicles, such as exosomes, which have an important role in cell-to-cell communication and tolerance, including cytokines, chemokines, membrane proteins, as well as mRNA and microRNA (miRNA). miRNA are small RNAs that act in gene regulation by binding to mRNAs and degrading them, in viral infections the miRNA can be used as biomarkers and/or act in cellular signaling pathways contributing or disadvantaging the antiviral response. There are still no reports about exosomes been capable of carrying viral particles, miRNAs and proteins that can contribute to viral dissemination in ZKV infection, especially across placental barrier. The Project proposes to evaluate exosomes from placental trophoblasts in their proteomic profile and miRNAs involved in the inflammatory response in ZKV infection. The research is going to be carried out in lineage cells of first trimester villous and extravillous trophoblasts and primary trophoblasts from health women term placentae to establish in vitro infection by ZKV and exosomes acquisition. The proteomic profile and viral antigens are going be analyzed in the exosomes of term placentae, infected or not with ZKV and Dengue virus type 1. It will also be performed the analysis of exosomes in the pro-inflammatory response and in the induction of cytokines in mononuclear cells from peripheral blood of women and newborns. In addiction, the expression profile of miRNA involved in regulating the inflammatory response in exosomes is going to be analyzed by PCR array (84 genes). These parameters can promote understanding of the presence of immunological or epigenetic changes in ZKV infection in relation to the mechanisms of tolerance in pregnancy. Furthermore, the components that lead to inflammation, been placental or systemic, can influence fetal neurological development in the presence of ZKV infection.

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