Instituto Evandro Chagas, Brazil; Universidade Federal do Pará, Brazil.
Instituto Evandro Chagas, Brazil.
Virology. 2024 Aug;596:110095. doi: 10.1016/j.virol.2024.110095. Epub 2024 May 1.
Dengue virus (DENV) is a major global health concern, causing millions of infections annually. Understanding the cellular response to DENV infection is crucial for developing effective therapies. This study provides an in-depth analysis of the cellular response to Dengue virus (DENV) infection, with a specific focus on the interplay between microRNAs (miRNAs), apoptosis, and viral load across different DENV serotypes. Utilizing a variety of cell lines infected with four DENV serotypes, the research methodically quantifies viral load, and the expression levels of miRNA-15, miRNA-16, and BCL2 protein, alongside measuring apoptosis markers. Methodologically, the study employs quantitative PCR for viral load and miRNA expression analysis, and Western blot for apoptosis and BCL2 detection, with a statistical framework that includes ANOVA and correlation analysis to discern significant differences and relationships. The findings reveal that despite similar viral loads across DENV serotypes, DENV-2 exhibits a marginally higher load. A notable upregulation of miRNA-15 and miRNA-16 correlates positively with increased viral load, suggesting their potential role in modulating viral replication. Concurrently, a marked activation of caspases 3 and 7, along with changes in BCL2 protein levels, underscores the role of apoptosis in the cellular response to DENV infection. Conclusively, the study enhances the understanding of miRNA involvement in DENV pathogenesis, highlighting miRNA-15 and miRNA-16 as potential regulatory agents in viral replication and apoptosis. These findings pave the way for further exploration into miRNA-based therapeutic strategies against DENV infection.
登革热病毒(DENV)是一个全球性的健康问题,每年导致数百万人感染。了解细胞对 DENV 感染的反应对于开发有效的治疗方法至关重要。本研究深入分析了细胞对登革热病毒(DENV)感染的反应,特别关注不同 DENV 血清型之间 microRNAs(miRNAs)、细胞凋亡和病毒载量的相互作用。利用四种 DENV 血清型感染的多种细胞系,该研究系统地量化了病毒载量、miRNA-15、miRNA-16 和 BCL2 蛋白的表达水平,以及测量细胞凋亡标志物。该研究采用定量 PCR 进行病毒载量和 miRNA 表达分析,Western blot 进行细胞凋亡和 BCL2 检测,统计学框架包括 ANOVA 和相关性分析,以确定显著差异和关系。研究结果表明,尽管不同 DENV 血清型的病毒载量相似,但 DENV-2 的载量略高。miRNA-15 和 miRNA-16 的显著上调与病毒载量的增加呈正相关,表明它们可能在调节病毒复制中发挥作用。同时,caspase 3 和 7 的激活以及 BCL2 蛋白水平的变化突出了细胞凋亡在 DENV 感染中的作用。总之,该研究增强了对 miRNA 在 DENV 发病机制中的作用的理解,强调了 miRNA-15 和 miRNA-16 作为病毒复制和细胞凋亡的潜在调节因子。这些发现为进一步探索 miRNA 为基础的 DENV 感染治疗策略铺平了道路。