Holistic characterization of the molecular mechanisms of T cell exhaustion in patients with ZIKA.

• Grant number: 25/07090-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Otávio Cabral Marques
• Grantee: Fernando Yuri Nery do Vale
• 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

During the acute phase of infection, T lymphocytes undergo activation and differentiation accompanied by robust proliferation. However, during chronic infections, there is a progressive loss of T cell response, a phenomenon known as T cell exhaustion.Among the characteristics of exhausted T cells are the upregulation and co-expression of multiple inhibitory receptors, reduced cytokine production, decreased proliferative capacity, and an altered epigenetic profile (e.g., demethylation of inhibitory receptor loci).Since most individuals infected with the Zika virus (ZIKV) are asymptomatic, we must consider that, in addition to the degree of virulence of viral strains (extrinsic factors), the immunological profile (intrinsic factors) of infected individuals also influences the development and progression of arboviral infections. Our hypothesis is that the severity of the patients' phenotype, particularly among those who are unable to efficiently eliminate ZIKV, is influenced by the individual's immune potential. In other words, individuals who are unable to effectively clear the virus present a deficit in T cell response. Thus, our objective is to analyze the mechanisms and molecular signature pathways that are common and specific regulators of the immune response to ZIKV, as well as the mechanisms underlying T cell exhaustion in patients with ZIKV.