Analysis of Differentially Expressed Novel MicroRNAs as Potential Biomarkers in Dengue Virus Type 1 Infection.

Abstract

Host-derived miRNAs are reported to play diverse roles in dengue virus (DENV) infection, but DENV-derived miRNAs have been rarely studied. Here, we used serum samples from three patients infected with dengue virus type 1 (DENV1) and three healthy volunteers to detect and profile novel microRNAs in dengue virus-infected human serum. MicroRNAs in serum samples were sequenced using an Illumina HiSeq 2000 system, and clean reads were trimmed, aligned, normalized, and analyzed to identify differentially expressed and novel microRNAs. Four microRNAs were selected as DENV1 infection biomarkers and verified through 1:2 paired case-control study, using serum from 15 DENV1-infected patients and 30 healthy volunteers. We identified 182 potential novel miRNAs, with 20 novel miRNAs found to have miRDeep2 score ≥ 4.0. Fifty-eight known and 11 novel miRNAs were upregulated at least 2-fold in DENV1-infected serum. Twenty-two known and 4 novel miRNAs were downregulated at least 0.5-fold. The AUCs of four selected miRNAs, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-novel-chr17_35150, and hsa-miR-novel-chr10_24390, were respectively: 0.962 (95% CI: 0.913 - 1.000, p > 0.05), 0.924 (95% CI: 0.851 - 0.998, p < 0.05), 0.941 (95% CI:0.877 - 1.000, p > 0.05), and 0.991 (95% CI: 0.973 - 1.000, p > 0.05). In summary, our study demonstrates that serum miRNA levels are affected by DENV1 infection, identifies novel DENV1-associated miRNAs, and suggests that Hsa-miR-122-5p may be a potential biomarker for DENV1 infection.