Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons

Abstract

MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection

“…Further studies involving larger patient groups, including pre-symptomatic, asymptomatic and mild (non-hospitalised) patients, in addition to different infections, are planned to assess whether this miRNA biomarker can improve COVID-19 detection rates. While the present study did not measure circulating miRNA profiles in patients infected with other respiratory viruses, published reports of circulating miR-NAs DE in influenza A and influenza B patients [36] show clear differences to COVID-19 patients. These findings, in addition to data from ferret infection trials in the present study, indicate that miRNA profiling may be able to classify different infection types.…”

Influenza Virus-Induced Novel miRNAs Regulate the STAT Pathway

“…The negative regulation of STAT3 by miR-20a via binding to the 3′-UTR of STAT3 mRNA was also demonstrated in pancreatic carcinoma cells [ 29 ]. We also have reported the increased expression of GCSF and IL-6 in influenza A and B patients’ serum [ 30 ]. In addition to these, put-miR-34 was recovered in AGO-immunoprecipitation complexes and from the mimic transfected cells ( Table 4 , Figure 5 ).…”

Macrophage-derived microRNA-223 Promotes Intestinal Mucosal Barrier Dysfunction via Exosomal Pathways in Inflammatory Bowel Disease

“…Liu et al reported that miR-381-3p inhibition enhanced intestinal epithelial proliferation and restored intestinal barrier function in intestinal I/R injury by suppression of its target gene nuclear receptor-related protein 1 (nurr1)-mediated proliferative pathway [31]. UC patients have higher expression of miR-24 in colonic biopsies and blood samples, which leads to a decrease in barrier integrity [32] MiRNAs encapsulated in exosomes are selectively and actively loaded, which is a key crosstalk mechanism in IBD regulation [33][34][35]. In many studies, receptor-binding proteins, known as membranous proteins, facilitate the selective packaging of miRNAs in many diseases [36,37].…”