DataSheet_1_Interferome signature dynamics during the anti-dengue immune response: a systems biology characterization.docx

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.

登革病毒（Dengue virus, DENV）感染可表现为发热性疾病，其病程包含三个明确阶段：早期急性相、晚期急性相及恢复期。登革的临床表现严重程度各异，可分为登革热、登革出血热及登革休克综合征三种类型。干扰素（Interferons, IFNs）是介导抗登革病毒免疫应答的核心抗病毒细胞因子。截至目前，登革患者体内I型、II型及III型干扰素调控基因（interferome，干扰素组）的独特全局特征仍未得到阐明。为此，本研究开展了一项深入的跨研究，对登革病毒感染相关的转录组数据进行整合分析。系统生物学分析结果显示，抗登革免疫应答的核心特征为大量干扰素调控基因（interferon-regulated genes, IRGs）的调控富集，例如细胞因子介导的信号通路（如I型、II型干扰素）及趋化作用；随后出现与细胞周期相关的基因转录浪潮，该过程同样受干扰素级联反应调控。通过对疾病分层潜力的辅助分析，并结合干扰素组的转录组荟萃分析，本研究筛选出IFI27、ISG15及CYBRD1等可作为疾病严重程度潜在有效生物标志物的基因。综上，本研究阐明了登革病毒感染中干扰素组特征的全貌，揭示出干扰素组的动态变化是抗登革免疫应答的关键核心组成部分。