Profile of microRNAs from the C19MC and C14MC family involved in the regulation of antiviral and inflammatory response in placentas in Chikungunya and Oropouche infection

• Grant number: 24/20447-4
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Maria Notomi Sato
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Viral infection during pregnancy can pose risks such as vertical transmission and serious consequences for the fetus. Prenatal infection with arboviruses such as chikungunya (CHIKV) can have serious consequences with neurological damage to the fetus. Oropouche virus (OROV), an emerging arbovirus, causes oropouche fever and recent reports in 2024 have identified cases of fetal death and severe microcephaly. Congenital infections increasingly require preventive and therapeutic interventions. To this end, it is necessary to understand the regulatory mechanisms involved at the maternal-fetal interface. MicroRNAs (miRs) are regulators of gene expression that have been implicated in several human pathologies, including those caused by viral infections. There are two major clusters of miRs enriched in the placenta, the chromosome 14 miR cluster (C14MC) and the chromosome 19 miR cluster (C19MC), which are associated with fetal development, immune defence and antiviral activity. Thus, it is proposed to analyse the miRs involved in the antiviral and inflammatory response to CHIKV and OROV infection at the maternal-fetal interface. The miRNOMA profile of placentas from pregnant women infected with CHIKV will be analysed in search of miRs with regulatory action of the antiviral and inflammatory response. OROV infection will be performed in placental villus explant cultures to analyse the expression of C19MC and C14MC family miRs. The selection of differentially expressed miRs (DEMs) will be analysed for interaction between miRs and target mRNA, and the DEM candidates will be analysed by miR interference using miR mimics and miR antagonists (antagomiRs) in trophoblastic lineage and in vivo in a model of pregnant mice infected with CHIVK and OROV. In addition, protein analysis of genes regulated by DEMs will be analysed in placental tissue from pregnant women infected with CHIKV and OROV. The profiling of miRNAs and antiviral/immune factors is important to characterise the dysfunctional immune response and to look for a correlate of protection with therapeutic potential against infections. (AU)