Comprehensive Characterization of Serum MicroRNA Profile in Response to the Emerging Avian Influenza A (H7N9) Virus Infection in Humans

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.

microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques

“…We also observed a trend of increased miR-146b expression, which was previously reported to be increased at 24 h postinfection in human lung epithelial cells (A549) following in vitro infection with H1N1 and H3N2 influenza virus (38,44). Additionally, our studies revealed that miR-20a and miR-451 were upregulated at 28 dpi in PBMCs as previously documented in serum (collected within 14 days from onset of infection) of patients infected with H7N9 influenza and at 8 h following in vitro H1N1 influenza infection of murine DCs, respectively (35,48,56). Our studies also showed elevated levels of miR-146b, which has previously been observed in whole blood (collected within 2 weeks from onset of infection) of patients infected with H1N1 (43).…”

miR-146a-5p promotes replication of infectious bronchitis virus by targeting IRAK2 and TNFRSF18

“…The mRNAs are mostly supposed to be regulated by miRNAs, which are a class of small non-coding RNAs that suppress the expression of target genes by binding to the 3′-untranslated regions (UTRs) [9]. Post infection of IBVs can encode miRNAs or influence the expression levels of cellular miRNAs [10,11]. miRNAs have been reported to play an important role in virus pathogenesis such as miR-122, which may be able to stabilize the HCV genomic RNA [12], and the immune response related miRNAs such as miR-130a, miR-155, miR-23b miR-146a-5p which can help the virus to augment its replication or in evasion of cellular immune response [13][14][15].…”

Scientific Advances in the Diagnosis of Emerging and Reemerging Viral Human Pathogens

“…Increasing evidence indicates that cell free miRNAs are present in body fluids including blood and saliva. They are produced endogenously in response to the molecular change in cells, and therefore they can be used as diagnostic reporters for various diseases such as cancer and viral infections (Zhu et al, 2014). MiRNA is a class of small (18À24 nucleotides in length) noncoding RNAs, which involves in gene regulation and plays important roles in cell proliferation, differentiation, apoptosis, and tumorigenesis (Kaladhar, 2015).…”