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

• Grant number: 16/06490-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): October 01, 2017
• Effective date (End): May 31, 2021
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Juliano de Paula Souza
• Host 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)

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)

STUBBS, SARAH HULSEY; PONTELLI, MARJORIE CORNEJO; MISHRA, NISCHAY; ZHOU, CHANGHONG; SOUZA, JULIANO DE PAULA; MENDES VIANA, ROSA MARIA; LIPKIN, W. IAN; KNIPE, DAVID M.; ARRUDA, EURICO; WHELAN, SEAN P. J.. esicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mic. MBIO, v. 12, n. 4, JUL-AUG 2021. (16/06490-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Juliano de Paula. Expression of microRNAs in trophoblasts infected \in vitro\ by Zika and Chikungunya viruses and experimental model of vertical transmission of Chikungunya virus in pregnancy and breastfeeding. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.