A Integrative systems analysis of the immune response to dengue virus

• Ano de defesa: 2024
• Autor(a) principal: Plaça, Desirée Rodrigues
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Autoimmunity; Autoimunidade; Biomarcadores; Biomarkers; Dengue virus; Immune response; Interferoma; Interferonome; Resposta imune; Systemic vaccinology; T cell exhaustion; Vacinologia sistêmica, Exaustão de células T; Vírus da dengue
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/9/9142/tde-10102024-104755/

Infection by the dengue virus (DENV) is a significant global health problem, characterized by a range of clinical manifestations that vary from asymptomatic to severe dengue and dengue shock syndrome. This thesis aims to systematically and integratively unravel the immune response to the dengue virus. We performed a comprehensive orthogonal analysis using high-throughput transcriptomic and proteomic data to uncover the molecular foundations of the immune response during different phases and severities of dengue infection. The findings highlight the crucial role of interferon-regulated genes (IRGs) in orchestrating the antiviral response, with distinct signatures identified for the early acute, late acute, and convalescent phases. This thesis explores the immune signatures induced by dengue vaccines, revealing similarities and differences with natural infections. Additionally, this work uncovers the exhaustive phenotypes of memory CD8+ T cells, elucidating the mechanisms of T cell exhaustion in dengue patients, and investigates the potential of the dengue virus to trigger immune responses associated with and mechanisms linked to the development of autoimmune diseases post-infection. Overall, this integrative analysis enhances our understanding of the immune response to DENV, offering insights into potential biomarkers for disease severity, informing vaccine development, and highlighting the complex interaction between viral infection and autoimmunity. The results indicate significant implications for improving diagnostic, therapeutic, and preventive strategies against dengue.