Investigation of the pathophysiological changes caused by the Measles Virus (MeV) in CNS cells derived from human induced pluripotent cells (hiPSC)

• Grant number: 24/22501-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: February 29, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Patricia Cristina Baleeiro Beltrão Braga
• Grantee: Debora Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/02895-0 - Investigation of the action of measles virus (MeV) on the nervous system: modeling the infection in neuroprogenitor cells, neurons, astrocytes, and brain organoids derived from induced pluripotent stem cells (iPSC)., AP.R

Abstract

Measles, caused by the measles virus (MeV), is a highly infectious disease associated with significant morbidity and mortality, particularly in developing countries. While primarily recognized for its effects on the respiratory and immune systems, MeV is also linked to severe neurological complications, such as encephalitis and subacute sclerosing panencephalitis (SSPE), which can result in irreversible neurological deficits. Despite the global reduction in cases following the introduction of effective vaccines, endemic outbreaks persist, highlighting the need for a deeper understanding of MeV pathogenesis, especially in the central nervous system (CNS).This study aims to investigate the pathophysiological effects of MeV infection on the CNS using an in vitro model derived from human-induced pluripotent stem cells (hiPSC). These cells offer a robust platform for studying viral infections, enabling the generation of CNS cell types such as neural progenitor cells (NPC), neurons, astrocytes, and brain organoids. The research will assess cytopathic effects, cell death pathways, production of pro-inflammatory cytokines, gene and protein expression, and neural functionality. Comparisons between the wild-type and vaccine strains of MeV will help elucidate differences in infection mechanisms and physiological impacts.Expected outcomes include the identification of cellular and molecular alterations caused by MeV infection, focusing on damage to neurogenesis, synaptogenesis, and the inflammatory response. Additionally, the study seeks to understand how specific viral mutations contribute to MeV persistence in the CNS and its pathological consequences. This project will contribute to neuroscience and virology, providing insights into MeV effects on the CNS and reinforcing the critical role of vaccination for the public health system for the prevention of neurological complications.