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).

• Grant number: 24/02895-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Medicine
• 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
• Associated researchers: Danielle Bruna Leal de Oliveira ; Edison Luiz Durigon
• Associated scholarship(s): 24/22501-6 - Investigation of the pathophysiological changes caused by the Measles Virus (MeV) in CNS cells derived from human induced pluripotent cells (hiPSC), BP.DR; 24/21462-7 - Investigation measles virus (MeV) action on brain organoids derived from induced pluripotent stem cells (iPSC), BP.TT

Abstract

Measles is an infectious disease caused by MeV, a virus of the Paramyxovirus family, genus Morbillivirus. MeV infection causes moderate to severe respiratory and gastrointestinal illness, skin rashes, and long-term immunosuppression, which makes the patient prone to opportunistic secondary infections. In addition, in some cases, the virus can persist in the body, which can lead to brain infection with the development of neurological outcomes such as measles inclusion body encephalitis (MIBE), which can occur years after the acute phase of the disease in an immunocompetent patient, and subacute sclerosing panencephalitis (SSPE), which develops several months after initial exposure in immunocompromised patients. Many aspects of measles pathogenesis and its neurological complications remain poorly understood and deserve more attention. The reprogramming technology generating induced pluripotent stem cells (iPSCs) has enabled the modeling of neurological diseases, with the production of functional CNS cells becoming an important strategy for better understanding the pathophysiological mechanisms of infectious agents in CNS cells. In this project, we propose to investigate the effects of MeV infection in NPC, neurons, astrocytes, and brain organoids derived from human induced pluripotent stem cells (hiPSC), thus contributing to the elucidation of the pathogenicity mechanisms used by the virus in the nervous system. Modeling nervous system diseases using human iPSC cells has proven to be a powerful tool for elucidating pathological and infectious processes in the nervous system and is advantageous over other models because it mimics viral infection in human tissues. (AU)