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The role of placental exosomes and microRNAs in the protection against the arboviruses Zika, Chikungunya and Oropouche

Grant number: 16/06490-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2017
Effective date (End): March 31, 2020
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Eurico de Arruda Neto
Grantee:Juliano de Paula Souza
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/02438-6 - Studies with Bunyaviridae that produce human disease, AP.TEM

Abstract

Due to geographic and environmental characteristics, Brazil is a country that favors the propagation of several arboviruses that infect humans, especially those transmitted by the bite of urban insects such as Aedes aegypti and Culicoides paraensis. A recent example was the emergence of Zika virus (ZIKV), which is rapidly spreading across the American continent, with a special impact in Brazil due to the occurrence of congenital syndromes, including microcephaly. Other arboviruses of epidemiological importance in Brazil are Chikungunya (CHIKV) and Oropouche (OROV). Data from the literature have already reported the vertical transmission and teratogenic effects induced by ZIKV and CHIKV in humans, and observations made during OROV outbreaks suggest that there is vertical transmission resulting in spontaneous abortion in infected women in early pregnancy. However, cellular and molecular mechanisms regarding transplacental congenital infection and the teratogenesis caused by these viruses are still not well understood and need to be studied. It has already been shown that microRNAs secreted via exosomes by placental trophoblastic cells are able to inhibit infection by certain DNA and RNA viruses. In the present project, we proposed the evaluation of alterations in the miRNA transcriptome of "in vitro" infected trophoblastic cells by ZIKV, CHIKV and OROV using large scale sequencing. It is also aimed to study how the inhibition of placental exosomes production alters the susceptibility and permissiveness of placental cells to these viruses. At the same time, exosomes purified from trophoblastic cells will be used to treat cells from different lineages in culture to analyze their antiviral effects. In addition, an evaluation of the vertical transmission of OROV in a Syrian hamster model will be performed, with analysis of teratogenic effects in the fetuses. (AU)