Evaluation of the Impact of Viral Neuroinfections on Synaptic Plasticity and Neurodevelopment in Cellular Models Derived from Induced Pluripotent Cells

• Grant number: 25/03479-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: January 31, 2030
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Patricia Cristina Baleeiro Beltrão Braga
• Grantee: Ana Luiza Moraes Octaviano
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Surveys on psychiatric and neurodevelopmental disorders have shown an exponential increase in recent years. This rise can be attributed not only to improved diagnostic capabilities but also to environmental factors, such as viral infections, which may play a significant role in this increase, thereby justifying the need for scientific investigation. In general, neurotropic viruses have the potential to affect the central nervous system (CNS), compromising synaptic plasticity and neurodevelopment, although the mechanisms involved in these processes are still poorly understood. Infections caused by the Zika virus have been particularly significant, as they are directly linked to alterations in neural development. However, other viruses, whose primary tropism is not the brain, have also proven disruptive to the homeostasis and functioning of the CNS, such as SARS-CoV-2 in acute and long COVID-19 cases, and the influenza virus in cases of encephalitis. Considering this, this project aims to investigate and compare the effects of SARS-CoV-2, Influenza A (IVA), and ZIKV viruses on the CNS, focusing particularly on changes in synaptic plasticity resulting from alterations in CNS function, to understand how these infections may contribute to neurodevelopmental disorders. To achieve this, the investigation will involve the use of brain organoids derived from induced pluripotent stem cells (iPSCs) of neurotypical individuals, which will be infected with the aforementioned viruses. In addition, we will compare infections in neurotypical organoids (controls) with infections in organoids derived from individuals with pre-existing neurodevelopmental disorders, such as autism spectrum disorder (ASD) and congenital Zika syndrome (CZS). In these cases, the goal is to examine the impact of infections on the developing CNS of these individuals, who have a genetic predisposition to outcomes such as ASD. The aim is to understand the mechanisms by which these infections alter synaptic plasticity, essential for neurodevelopment and cognitive functions, as it is sensitive to external disturbances. It is expected that specific alterations in neurodevelopment caused by these viruses will be identified, contributing to a better understanding of the relationship between these infections and neuropsychiatric disorders. This knowledge may, in turn, provide a foundation for new therapeutic approaches and public health strategies to mitigate the impacts of viral neuroinfections. (AU)