microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection

Author(s)

Polonio, Carolina M. ; da Silva, Patrick ; Russo, Fabiele B. ; Hyppolito, Brendo R. N. ; Zanluqui, Nagela G. ; Benazzato, Cecilia ; Beltrao-Braga, Patricia C. B. ; Muxel, Sandra M. ; Peron, Jean Pierre S.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 18, p. 19-pg., 2022-09-01.

Abstract

Viral infections have always been a serious burden to public health, increasing morbidity and mortality rates worldwide. Zika virus (ZIKV) is a flavivirus transmitted by the Aedes aegypti vector and the causative agent of severe fetal neuropathogenesis and microcephaly. The virus crosses the placenta and reaches the fetal brain, mainly causing the death of neuronal precursor cells (NPCs), glial inflammation, and subsequent tissue damage. Genetic differences, mainly related to the antiviral immune response and cell death pathways greatly influence the susceptibility to infection. These components are modulated by many factors, including microRNAs (miRNAs). MiRNAs are small noncoding RNAs that regulate post-transcriptionally the overall gene expression, including genes for the neurodevelopment and the formation of neural circuits. In this context, we investigated the pathways and target genes of miRNAs modulated in NPCs infected with ZIKV. We observed downregulation of miR-302b, miR-302c and miR-194, whereas miR-30c was upregulated in ZIKV infected human NPCs in vitro. The analysis of a public dataset of ZIKV-infected human NPCs evidenced 262 upregulated and 3 downregulated genes, of which 142 were the target of the aforementioned miRNAs. Further, we confirmed a correlation between miRNA and target genes affecting pathways related to antiviral immune response, cell death and immune cells chemotaxis, all of which could contribute to the establishment of microcephaly and brain lesions. Here, we suggest that miRNAs target gene expression in infected NPCs, directly contributing to the pathogenesis of fetal microcephaly. (AU)

• FAPESP's process: 20/06145-4 - Immunopathogenesis of COVID-19 in experimental models and nasal vaccine anti-SARS-CoV-2
• Grantee: Jean Pierre Schatzmann Peron
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/11828-0 - Evaluation of the microRNAs role in the immunopathogenesis of microcephaly caused by Zika virus in experimental models
• Grantee: Carolina Manganeli Polonio
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/26170-0 - Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/01717-2 - Resistance and susceptibility in Congenital Zika Virus Syndrome
• Grantee: Patrick da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/16748-8 - INVESTIGATION OF ZIKA VIRUS ACTION IN CENTRAL NERVOUS SYSTEM CELLS: MODELING INFECTION IN HUMAN ASTROCYTES DERIVED FROM INDUCED PLURIPOTENT CELLS
• Grantee: Patricia Cristina Baleeiro Beltrão Braga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/22504-1 - TAM receptors and their ligands Gas6 and Pros1 on the ZIKV Congenital Syndrome in Experimental Models
• Grantee: Jean Pierre Schatzmann Peron
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/00291-4 - Function of long-noncoding RNAs and microRNAs in the immune response and metabolism during Leishmania infection and the interference in the metabolism as new therapeutic strategy
• Grantee: Sandra Marcia Muxel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/07371-2 - Characterization of the role of T CD8+ lymphocytes in Zika virus infection
• Grantee: Nagela Ghabdan Zanluqui
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/13731-0 - MicroRNAs, neurodevelopment and antiviral immune response: how they can be connected?
• Grantee: Carolina Manganeli Polonio
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate