Interferome signature dynamics during the anti-dengue immune response: a systems biology characterization

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Usuda, Julia Nakanishi ; Placa, Desiree Rodrigues ; Fonseca, Dennyson Leandro M. ; Marques, Alexandre H. C. ; Filgueiras, Igor Salerno ; Chaves, Victor Gabriel Bastos ; Adri, Anny Silva ; Torrentes-Carvalho, Amanda ; Hirata, Mario Hiroyuki ; Freire, Paula Paccielli ; Catar, Rusan ; Cabral-Miranda, Gustavo ; Schimke, Lena F. ; Moll, Guido ; Cabral-Marques, Otavio

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 14, p. 16-pg., 2023-08-10.

Resumo

Dengue virus (DENV) infection manifests as a febrile illness with three distinct phases: early acute, late acute, and convalescent. Dengue can result in clinical manifestations with different degrees of severity, dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Interferons (IFNs) are antiviral cytokines central to the anti-DENV immune response. Notably, the distinct global signature of type I, II, and III interferon-regulated genes (the interferome) remains uncharacterized in dengue patients to date. Therefore, we performed an in-depth cross-study for the integrative analysis of transcriptome data related to DENV infection. Our systems biology analysis shows that the anti-dengue immune response is characterized by the modulation of numerous interferon-regulated genes (IRGs) enriching, for instance, cytokine-mediated signaling (e.g., type I and II IFNs) and chemotaxis, which is then followed by a transcriptional wave of genes associated with cell cycle, also regulated by the IFN cascade. The adjunct analysis of disease stratification potential, followed by a transcriptional meta-analysis of the interferome, indicated genes such as IFI27, ISG15, and CYBRD1 as potential suitable biomarkers of disease severity. Thus, this study characterizes the landscape of the interferome signature in DENV infection, indicating that interferome dynamics are a crucial and central part of the anti-dengue immune response. (AU)

• Processo FAPESP: 20/16246-2 - Caracterização holística do mecanismo de exaustão dos linfócitos T em pacientes com Zika
• Beneficiário: Dennyson Leandro Mathias da Fonseca
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/11710-2 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com Dengue
• Beneficiário: Desirée Rodrigues Plaça
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 23/03841-8 - Investigação holística e funcional das redes de interações neuroimunes durante a fisiopatologia de infecções virais neuroinvasivas
• Beneficiário: Victor Gabriel Bastos Chaves
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/18886-9 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 21/03675-5 - Análise da rede de moléculas associadas ao IFN em pacientes com dengue
• Beneficiário: Júlia Nakanishi Usuda
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica