INVESTIGATION OF ZIKA VIRUS ACTION IN CENTRAL NERVOUS SYSTEM CELLS: MODELING INFECTION IN HUMAN ASTROCYTES DERIVED FROM INDUCED PLURIPOTENT CELLS

• Grant number: 18/16748-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2018
• End date: May 31, 2021
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Patricia Cristina Baleeiro Beltrão Braga
• Grantee: Patricia Cristina Baleeiro Beltrão Braga
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Cecília Benazzato ; Cristine Marie Yde Ohki ; Danielle Bruna Leal de Oliveira ; Edison Luiz Durigon ; Fabiele Baldino Russo ; Helder Takashi Imoto Nakaya ; Jean Pierre Schatzmann Peron ; Paolo Marinho de Andrade Zanotto ; Paulo Emílio Corrêa Leite

Abstract

The Zika virus (ZIKV) is a flavivirus capable of causing infection in humans after the bite by mosquitoes of the genus Aedes contaminated with the virus. In 2015, the Brazilian strain of this virus - ZIKVBR caused an epidemic in Brazil, causing a congenital infection with the generation of several cases of cerebral malformation in infants of mothers infected by ZIKVBR. Through the study of neural progenitor cells, neurons and organoids derived from induced pluripotent stem cells (iPSC), our group and other researchers revealed the neurotrophism of ZIKVBR and helped to clarify their relationship with the Central Nervous System (CNS), showing that these cells are significantly affected by the infection. In this project, we propose to analyze biologically the effects of ZIKVBR infection in astrocyte cell culture, which are glial cells extremely important for homeostatic maintenance of neurons, also acting in inflammation of CNS. To do so, we will use astrocytes produced from human iPSCs and verify aspects of cell morphology and physiology, as well as gene and protein expression after infection with the virus. We thus hope to aid in elucidating the mechanisms used by the virus in pathogenicity caused in the CNS. (AU)

Scientific publications

(9)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

YDE OHKI, CRISTINE MARIE; BENAZZATO, CECILIA; RUSSO, FABIELE BALDINO; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA. Developing animal models of Zika virus infection for novel drug discovery. EXPERT OPINION ON DRUG DISCOVERY, v. 14, n. 6, APR 2019. (18/16748-8, 16/02978-6)

ROSA-FERNANDES, LIVIA; CUGOLA, FERNANDA RODRIGUES; RUSSO, FABIELE BALDINO; KAWAHARA, REBECA; DE MELO FREIRE, CAIO CESAR; CORREA LEITE, PAULO EMLIO; BASSI STERN, ANA CAROLINA; ANGELI, CLAUDIA BLANES; LEAL DE OLIVEIRA, DANIELLE BRUNA; MELO, STELLA REZENDE; et al. Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 13, MAR 15 2019. (16/02978-6, 14/06863-3, 13/08844-3, 18/16748-8, 11/20683-0, 15/02866-0)

DIAS, THOMAZ LUSCHER; SCHUCH, VIVIANE; BALEEIRO BELTRAO-BRAGA, PATRICIA CRISTINA; MARTINS-DE-SOUZA, DANIEL; BRENTANI, HELENA PAULA; FRANCO, GLORIA REGINA; NAKAYA, HELDER IMOTO. Drug repositioning for psychiatric and neurological disorders through a network medicine approach. TRANSLATIONAL PSYCHIATRY, v. 10, n. 1, MAY 12 2020. (17/25588-1, 18/03673-0, 14/10068-4, 19/00098-7, 18/16748-8)

LEITE, PAULO EMILIO CORREA; PORTES, JULIANA DE ARAUJO; PEREIRA, MARIANA RODRIGUES; RUSSO, FABIELE BALDINO; MARTINS-DUARTE, ERICA S.; DOS SANTOS, NATHALIA ALMEIDA; ATTIAS, MARCIA; BARRANTES, FRANCISCO J.; BELTRAO-BRAGA, PATRICIA CRISTINA BALEEIRO; DE SOUZA, WANDERLEY. Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 11, p. 11-pg., 2021-02-01. (16/02978-6, 18/16748-8)

BENAZZATO, CECILIA; RUSSO, FABIELE BALDINO; BELTRAO-BRAGA, PATRICIA CRISTINA BALEEIRO. An update on preclinical pregnancy models of Zika virus infection for drug and vaccine discovery. EXPERT OPINION ON DRUG DISCOVERY, v. 17, n. 1, SEP 2021. (18/16748-8, 16/02978-6)

RUSSO, FABIELE B.; TOLEDO, CARMEN M.; TOCANTINS, FERNANDO R.; SOUZA, GIOVANNA V.; BELTRAO-BRAGA, PATRICIA C. B.. ZIKV Teratogenesis: Clinical Findings in Humans, Mechanisms and Experimental Models. FRONTIERS IN VIROLOGY, v. 1, p. 7-pg., 2022-03-11. (16/02978-6, 18/16748-8)

OHKI, CRISTINE MARIE YDE; BENAZZATO, CECILIA; VAN DER LINDEN, VANESSA; FRANCA, JULIA, V; TOLEDO, CARMEN M.; MACHADO, RAFAEL RAHAL GUARAGNA; ARAUJO, DANIELLE BASTOS; OLIVEIRA, DANIELLE BRUNA LEAL; NERIS, ROMULO S.; ASSUNCAO-MIRANDA, IRANAIA; et al. Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1870, n. 5, p. 13-pg., 2024-04-17. (13/08844-3, 18/16748-8, 17/24769-2, 11/20683-0, 16/02978-6, 16/20045-7, 17/27131-9)

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)

BRITO, ANITA; FRANCO, FELIPE; BRENTANI, HELENA; BELTRAO-BRAGA, PATRICIA CRISTINA BALEEIRO. Assessment of vulnerability dimensions considering Family History and environmental interplay in Autism Spectrum Disorder. BMC Psychiatry, v. 23, n. 1, p. 13-pg., 2023-04-14. (16/02978-6, 18/16748-8)