Dengue presents a wide clinical spectrum. Most patients recover following a self-limiting non-severe clinical course. A small proportion of patients progress to severe disease, mostly characterized by plasma leakage with or without hemorrhage. Early symptoms of severe dengue (SD) are similar to those of non-severe dengue fever (DF). Severe symptoms manifest after 3–5 days of fever, which can be life threatening due to lack of proper medications and inability to distinguish severe cases during the early stages. Early prediction of SD in patients with no warning signs who may later develop severe infection is very important for proper disease management to alleviate related complications and mortality. microRNA are small non-coding RNA molecules that regulate post-transcriptional gene expression. Due to the remarkable stability and the role of microRNA in gene expression, altered expression of microRNA was evaluated to explore clinically relevant prognostic markers of severe dengue. The relative expression of microRNA hsa-let-7e (let-7e), hsa-miR-30b-5p (miR-30b), hsa-miR-30e-3p (miR-30e), hsa-miR-33a (miR-33a), and hsa-miR-150-5p (miR-150) and several putative target genes in peripheral blood cells (PBC) collected from 20 DF and 20 SD positive patients within 4 days from fever onset was evaluated by quantitative reverse transcription PCR (qRT-PCR). miR-150 showed significant (P < 0.01) up regulation in PBC of SD patients compared to DF patients during the acute phase of infection. Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection. Differential expression of microRNA miR-150 and the putative target gene EZH2 may serve as reliable biomarkers of disease severity during early stages of dengue infection.

中文翻译：

---

microRNA，miR-150和zeste同源物2（EZH2）增强子在外周血细胞中的差异表达作为严重登革热的早期预后标志物

登革热具有广泛的临床范围。大多数患者会按照自我限制的非严重临床过程进行康复。一小部分患者发展为严重疾病，主要特征是血浆渗漏伴有或没有出血。严重登革热（SD）的早期症状类似于非严重登革热（DF）的症状。发烧3–5天后会出现严重症状，由于缺乏适当的药物以及在早期阶段无法区分严重病例，可能危及生命。对于没有警告征兆的患者进行SD的早期预测，之后可能发展为严重感染，对于适当的疾病管理以减轻相关的并发症和死亡率非常重要。microRNA是调节转录后基因表达的小型非编码RNA分子。由于microRNA在基因表达中具有显着的稳定性和作用，因此对microRNA的表达变化进行了评估，以探索重症登革热的临床相关预后标志物。microRNA hsa-let-7e（let-7e），hsa-miR-30b-5p（miR-30b），hsa-miR-30e-3p（miR-30e），hsa-miR-33a（miR- 33a），并通过定量逆转录PCR对hsa-miR-150-5p（miR-150）和发烧后4天内从20例DF和20例SD阳性患者收集的外周血细胞（PBC）中的几个假定靶基因进行了评估（qRT-PCR）。在感染的急性期，与DF患者相比，miR-150在SD患者的PBC中显示出明显的上调（P <0.01）。Zeste同源2（EZH2）的增强子的表达是显着（P <0。01）下调，表明在感染的早期阶段，SD患者中也参与了表观遗传调控的基因的差异表达。microRNA miR-150和推定的靶基因EZH2的差异表达可以作为登革热感染早期疾病严重程度的可靠生物标志物。