Impact of Pandemic Respiratory Viruses Influenza A and SARS-CoV-2 on Mitochondrial Function in Lymphoid Tissues

• Grant number: 24/06237-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Diana Mota Toro
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/26119-0 - Emerging and re-emerging viruses: biology, pathogenesis and prospection, AP.TEM

Abstract

The seasonal recurrence of viral respiratory diseases, such as Influenza A, and the increasing incidence of SARS-CoV-2 represent significant challenges in understanding the mechanisms underlying persistent viral infections. Mitochondrial dysfunctions may compromise the immune response, facilitating chronic infections. The S1PR1 receptor plays a crucial role in T cell response and mitochondrial fission. Additionally, extracellular vesicles containing mitochondrial components play an important role in intercellular communication. Our goal is to investigate the impact of influenza A and SARS-CoV-2 infections on the metabolism and mitochondrial function of tonsillar lymphomononuclear cells in natural infection compared to in vitro infection and the MucilAir model, with emphasis on the following innovative aspects: Characterization of mitochondrial morphology, activity, and metabolic profile by Seahorse XF and its association with the phenotype and function of macrophage, T and B lymphocyte subpopulations, characterized by flow cytometry; Evaluation of the influence of the S1PR1 receptor on mitochondrial activity; Purification of MitoVEs by ultracentrifugation and their characterization by Nanotrack (NTA), transmission electron microscopy (TEM), MitoTracker, western blot, and/or flow cytometry on a CytoFlex. This study has the potential to generate understanding of viral persistence and the role of the virome in lymphohematopoietic tissues, contributing to the understanding of virus-immunometabolism interaction. The use of human tonsil cells as an in vitro model is crucial due to their physiological relevance, providing insights into viral persistence in secondary lymphoid tissue and immunological responses. (AU)