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

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)