Ferreira Cristina Santos, Da Silva Alan Tardin, Brustolini Otávio José Bernandes, Soares Beatriz Rodrigues Pellegrina, Manuli Erika Regina, Ramundo Mariana Severo, Paranhos-Baccala Glaucia, Sabino Ester Cerdeira, Vasconcelos Ana Tereza Ribeiro
Laboratório de Bioinformática, Laboratório Nacional de Computação Científica (LNCC/MCTIC), Rio de Janeiro, Brazil.
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Front Immunol. 2025 Mar 7;16:1557588. doi: 10.3389/fimmu.2025.1557588. eCollection 2025.
Human Endogenous Retroviruses (HERVs), which can be activated by viral infections, have complex roles in gene regulation and immune modulation. However, their contribution to disease progression is not yet fully understood. Dengue fever ranges from mild symptoms to severe cases characterized by plasma leakage and immune dysregulation, providing a relevant context to investigate these interactions.
This study comes up with a comprehensive analysis of differentially expressed HERVs (DE-HERVs), protein-coding genes (DEGs), and regulatory elements such as microRNAs (DE-miRNA) and non-LTR retroviruses (DE-LINEs and DE-SINEs) derived from the transcriptomes of Brazilian dengue patients across different disease stages.
The results show that DE-HERVs are associated with key genes identified in severe dengue cases, including , , , and , suggesting their role in immune modulation and endothelial permeability. Specifically, the upregulation of and genes in patients who progressed to severe dengue correlates with a complex regulatory network involving down-regulated microRNAs (miRNAs) and non-LTR retroviruses, emphasizing their relevance to inflammation and vascular permeability. MicroRNAs and non-LTR retroviruses were found to regulate these genes differently across dengue stages, with non-LTR elements appearing predominantly in non-severe cases and miRNA expression profiles varying across the comparison groups.
These findings improve our understanding of the molecular mechanisms underlying dengue progression and suggest that HERV-related regulatory networks may influence viral infections. Further research is required to clarify the specific roles of HERVs in dengue pathogenesis.
人类内源性逆转录病毒（HERVs）可被病毒感染激活，在基因调控和免疫调节中具有复杂作用。然而，它们对疾病进展的贡献尚未完全明确。登革热症状从轻微到严重不等，严重病例以血浆渗漏和免疫失调为特征，为研究这些相互作用提供了相关背景。
本研究对来自巴西登革热患者不同疾病阶段转录组的差异表达人类内源性逆转录病毒（DE-HERVs）、蛋白质编码基因（DEGs）以及调控元件（如微小RNA（DE-miRNA）和非长末端重复逆转录病毒（DE-LINEs和DE-SINEs））进行了全面分析。
结果表明，DE-HERVs与重症登革热病例中鉴定出的关键基因相关，包括[具体基因名称未给出]，提示它们在免疫调节和内皮通透性方面的作用。具体而言，进展为重症登革热的患者中[具体基因名称未给出]基因的上调与一个涉及微小RNA（miRNAs）下调和非长末端重复逆转录病毒的复杂调控网络相关，强调了它们与炎症和血管通透性的相关性。发现微小RNA和非长末端重复逆转录病毒在登革热各阶段对这些基因的调控方式不同，非长末端重复元件主要出现在非重症病例中，且微小RNA表达谱在各比较组中有所不同。
这些发现增进了我们对登革热进展潜在分子机制的理解，并表明与HERV相关的调控网络可能影响病毒感染。需要进一步研究以阐明HERVs在登革热发病机制中的具体作用。
