Evaluation of the microRNAs role in the immunopathogenesis of microcephaly caused by Zika virus in experimental models

• Grant number: 17/11828-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2017
• Effective date (End): December 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jean Pierre Schatzmann Peron
• Grantee: Carolina Manganeli Polonio
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/13731-0 - MicroRNAs, neurodevelopment and antiviral immune response: how they can be connected?, BE.EP.DR

Abstract

Viral infections have always been the cause of serious human diseases usually increasing rates of morbidity and mortality worldwide. Recently, a flavivirus transmitted by the Aedes aegypti vector, called Zika virus (ZIKV) was introduced in South America, causing a major public health problem. Initially it was not considered a threat to human health, with few cases reported mainly in Africa and Asia. However, in 2007 and 2014, outbreaks occurred in Micronesia and French Polynesia respectively, evidencing this as a potential pathogen of clinical importance. On February 1st, 2016 the World Health Organization (WHO) declared a state of global emergency after the alarming increase in the number of babies born with microcephaly and adults with Guillain Barré syndrome in our country, both related to the infection. Recent works have shown that the virus is able to cross a placenta and reach the fetal brain, mainly causing the death of neuronal precursor cells and subsequent reduction of the brain and cranial measurements. Genetic differences, mainly related to type I IFN, may greatly influence the susceptibility to infection. These molecules interact with their IFNAR receptor, triggering athe expression of IFNs stimulated genes (ISGs). ISGs contemplate many important molecules that blocks the viral replication cycle, through the synthesis of lytic proteins or even through the induction of cell death. ISGs can also be modulated by a number of other factors through post-transcriptional mechanisms and, in this context, miRNAs may play a key role. However, still very little is known about the involvement of miRNAs in this infection. In this context, in this project we aim to elucidate the role of miRNAs in the experimental infection by ZIKV and, mainly, relating their target genes with the establishment of microcephaly and cerebral lesions. We will use experimental approaches in vitro using cells of the central nervous system and in vivo, with SJL animals susceptible to infection. The results obtained will help to elucidate the immunopathogenic mechanisms of microcephaly caused by ZIKV.

Scientific publications

(6)

(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)

GIOVANNONI, FEDERICO; BOSCH, IRENE; POLONIO, CAROLINA MANGANELI; TORTI, MARIA F.; WHEELER, MICHAEL A.; LI, ZHAORONG; ROMORINI, LEONARDO; RODRIGUEZ VARELA, MARIA S.; ROTHHAMMER, VEIT; BARROSO, ANDREIA; et al. AHR is a Zika virus host factor and a candidate target for antiviral therapy. NATURE NEUROSCIENCE, v. 23, n. 8, JUL 2020. (17/11828-0, 17/22504-1, 16/07371-2, 17/26170-0)

POLONIO, CAROLINA MANGANELI; DE FREITAS, CARLA LONGO; DE OLIVEIRA, MARILIA GARCIA; ROSSATO, CRISTIANO; BRANDAO, WESLEY NOGUEIRA; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; NISHIYAMA MIMURA, LUIZA AYUMI; BARROS SILVA, MAYSA BRAGA; GARCIA CALICH, VERA LUCIA; et al. Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression. Clinical Science, v. 135, n. 9, p. 1065-1082, MAY 2021. (18/10242-5, 17/22504-1, 17/11828-0, 16/07371-2, 17/26170-0)

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.. microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 18, p. 19-pg., 2022-09-01. (20/06145-4, 17/11828-0, 17/26170-0, 21/01717-2, 18/16748-8, 17/22504-1, 22/00291-4, 16/07371-2, 19/13731-0)

DE FREITAS, CARLA LONGO; POLONIO, CAROLINA MANGANELI; BRANDAO, WESLEY NOGUEIRA; ROSSATO, CRISTIANO; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; DE OLIVEIRA, MARILIA GARCIA; EVANGELISTA, LUCILA PIRES; HALPERN, SILVIO; MALUF, MARIANGELA; et al. Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System. STEM CELL REVIEWS AND REPORTS, AUG 2021. (20/06145-4, 16/07371-2, 18/10242-5, 17/11828-0, 17/22504-1, 17/26170-0)

POLONIO, CAROLINA MANGANELI; PERON, JEAN PIERRE SCHATZMANN. ZIKV Infection and miRNA Network in Pathogenesis and Immune Response. Viruses-Basel, v. 13, n. 10, OCT 2021. (19/13731-0, 17/26170-0, 20/06145-4, 17/11828-0, 17/22504-1)

SILVA-FILHO, JOAO LUIZ; DE OLIVEIRA, LILIAN G.; MONTEIRO, LETICIA; PARISE, PIERINA L.; ZANLUQUI, NAGELA G.; POLONIO, CAROLINA M.; DE FREITAS, CARLA L.; TOLEDO-TEIXEIRA, DANIEL A.; DE SOUZA, WILLIAM M.; BITTENCOURT, NAJARA; et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. BRAIN BEHAVIOR AND IMMUNITY, v. 97, p. 260-274, OCT 2021. (17/26908-0, 16/00194-8, 20/02159-0, 16/21259-0, 18/13866-0, 16/12855-9, 17/22062-9, 17/26170-0, 17/11828-0, 17/02402-0, 20/02448-2, 18/13645-3, 16/07371-2)

Academic Publications

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

POLONIO, Carolina Manganeli. Evaluation of microRNAs in the immunopathogenesis of microcephaly caused by Zika virus in experimental models. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.