Holistic and functional investigation of the neuroimmune interactions networks during the pathophysiology of neuroinvasive viral infections

• Grant number: 23/03841-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2023
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Otávio Cabral Marques
• Grantee: Victor Gabriel Bastos Chaves
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections, AP.JP

Abstract

Viral infections affecting the Central Nervous System (CNS) represent an emergent cause of illness and mortality in Brazil and worldwide. The emergence, re-emergence, and dysfunctions associated with neuroglial infections by viruses with neurotropic properties, such as ZIKV and DENV flaviviruses, SARS-CoV-2 and Rabies Virus (RABV), justify the need to understand the commonality and differences in the mechanisms by which the CNS coordinates immune responses across different phenotypes of infections. Thus, when integratively and functionally investigating the modules of central and systemic neuroimmunological interactions during the pathophysiology of neurotropic viral diseases, we will predict crucial pathways of neural regulation of immune responses upon infection of the brain parenchyma, as well as help to identify innovative modulating mechanisms of neuroimmunological functions. Therefore, the aim of this work is to holistically and functionally investigate the networks of neuroimmune interactions during the pathophysiology of neural infections by ZIKV, DENV, SARS-CoV-2, and RABV. A priori, a systemic analysis of raw RNA-Seq and microarray datasets of human or experimental samples deposited on the Gene Expression Omnibus (GEO) platform or in articles published in indexed journals will be performed, using bioinformatics technics, for the evaluation of the network of genes and biological pathways associated with neuroimmune functions that will support the functional validation of the project. Second, we will use a primary neuroglial infection model to functionally characterize the in vitro or in vitro expression of these markers. Given the severity of infections that affect the homeostasis of the Central Nervous System and the recent emergence of neuroimmunology, describing the regulatory mechanisms between these important systems will be fundamental to exploring new perspectives on the pathophysiology of infections that affect neural tissue.