Abstract
A novel avian-origin influenza A (H7N9) virus recently occurred in China and caused 137 human infection cases with a 32.8% mortality rate. Although various detection procedures have been developed, the pathogenesis of this emerging virus in humans remains largely unknown. In this study, we characterized serum microRNA (miRNA) profile in response to H7N9 virus infection using TaqMan Low Density Arrays. Upon infection, a total of 395 miRNAs were expressed in the serum pool of patients, far beyond the 221 in healthy controls. Among the 187 commonly expressed miRNAs, 146 were up-regulated and only 7 down-regulated in patients. Further analysis by quantitative RT-PCR revealed that the serum levels of miR-17, miR-20a, miR-106a and miR-376c were significantly elevated in patients compared with healthy individuals (p < 0.05). Receiver operating characteristic (ROC) curves were constructed to show that each miRNA could discriminate H7N9 patients from controls with area under the curve (AUC) values ranging from 0.622 to 0.898, whereas a combination of miR-17, miR-20a, miR-106a and miR-376c obtained a higher discriminating ability with an AUC value of 0.96. Our findings unravel the significant alterations in serum miRNA expression following virus infection and manifest great potential of circulating miRNAs for the diagnosis of viral diseases.
Highlights
A novel avian-origin influenza A H7N9 virus recently emerged in eastern China and was associated with three fatal human cases [1]
During the outbreak of H7N9 virus infection, a total of 57 participants were enrolled in our study, including 36 healthy controls (19 men and 17 women, mean age: 48.6 ± 11.6) and 21 patients (13 men and 8 women, mean age: 51.9 ± 18.7), of which 10 participants from each group were selected for the TaqMan Low Density Array assays
When the serum levels of these four miRNAs were subjected to combined analysis by multiple logistic regression, the generated Receiver operating characteristic (ROC) curve reflected a higher ability to differentiate patients with H7N9 virus infection from healthy controls (AUC value: 0.96; 95% confidence intervals (CI): 0.917–1.000), demonstrating the diagnostic accuracy of miR-17, miR-20a, miR-106a and miR-376c as effective biomarkers in combination (Figure 4)
Summary
A novel avian-origin influenza A H7N9 virus recently emerged in eastern China and was associated with three fatal human cases [1]. Bioinformatic prediction indicates that over 30% of all protein-coding genes may be regulated by miRNAs in mammals [6], emphasizing the potential significance of miRNAs as major post-transcriptional regulators These endogenous small RNAs have already been shown to play important roles in diverse biological events, such as development, proliferation, differentiation, apoptosis and tumor development [7,8]. Circulating miRNAs are usually packaged into exosome-like microparticles that can protect them against endogenous RNase digestion, and are highly stable in body fluids [15] This unique advantage has made them as ideal and powerful biomarkers for the diagnosis of Alzheimer’s disease [16], diabetes [17], cardiovascular disease [18]. We globally analyzed the serum miRNA expression profile in response to H7N9 virus infection in humans and further evaluated the diagnostic potential of circulating miRNA candidates
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