Dysregulated microRNA expression in serum of non-vaccinated children with varicella

Abstract

Circulating microRNAs (miRNAs) may play an important role in pathogen-host interactions and can serve as molecular markers for the detection of infectious diseases. To date, the relationship between circulating miRNAs and varicella-zoster virus (VZV) caused varicella has not been reported. Using TaqMan Low-Density Array (TLDA) analysis, expression levels of miRNAs in serum samples from 29 patients with varicella and 60 patients with Bordetella pertussis (BP), measles virus (MEV) and enterovirus (EV) were analyzed. The array results showed that 247 miRNAs were differentially expressed in sera of the varicella patients compared with healthy controls (215 up-regulated and 32 down-regulated). Through the following qRT-PCR confirmation and receiver operational characteristic (ROC) curve analysis, five miRNAs (miR-197, miR-629, miR-363, miR-132 and miR-122) were shown to distinguish varicella patients from healthy controls and other microbial infections with moderate sensitivity and specificity. A number of significantly enriched pathways regulated by these circulating miRNAs were predicted, and some of them were involved in inflammatory response, nervous system and respiratory system development. Our results, for the first time, revealed that a number of miRNAs were differentially expressed during VZV infection, and these five serum miRNAs have great potential to serve as biomarkers for the diagnosis of VZV infection in varicella patients.

Figure 1

Eight serum miRNA levels in varicella patients and healthy controls were selected for verification using real-time qRT-PCR in individual varicella patients (N = 29) and healthy controls (N = 43). Serum levels of miR-197, miR-363, miR-629, miR-132 and miR-122 were significantly higher in varicella patients compared with those in the control group (**, p < 0.01), while no significant differences were detected in the expression of miR-500, miR-10a and miR-491-5p. Expression levels of the miRNAs are normalized to cel-miR-238 (Log₂ relative level).

Figure 2

Receive operating characteristic (ROC) curves of differentially expressed miRNAs between varicella patients and healthy controls. ROC curves of miR-197 (A); miR-363 (B); miR-629 (C); miR-132 (D) and miR-122 (E) showed a moderate distinguishing efficiency. The combination of the five miRNAs showed a slightly higher AUC value of 0.872 (F).