Abstract
Human adenovirus (Adv) infection is responsible for most community-acquired pneumonia in infants and children, which results in significant morbidity and mortality in children every year. MicroRNAs (miRNAs) are associated with viral replication and host immune response. Knowing the miRNA expression profile will help understand the role of miRNAs in modulating the host response to adenovirus infection and possibly improve the diagnosis of adenovirus-infected pneumonia. In our study, total RNA extracted from whole blood of adenovirus-infected pneumonia children and healthy controls were analyzed by small RNA deep sequencing. Expression profiles of whole blood microRNAs were altered and distinctly different in adenovirus-infected children. The top 3 upregulated miRNA (hsa-miR-127-3p, hsa-miR-493-5p, and hsa-miR-409-3p) were identified in adenovirus-infected children and provided a clear distinction between infected and healthy individuals. Potential host target genes were predicated and validated by qRT-PCR to study the impact of microRNAs on the host genes. Most of the target genes were involved in the MAPK signaling pathway and innate immune response. These highly upregulated microRNAs may have crucial roles in Adv pathogenesis and are potential biomarkers for adenovirus-infected pneumonia.
Highlights
Human adenovirus (Adv) infection is responsible for most community-acquired pneumonia in infants and children [1, 2]
To study the impact of Adv infection on cellular small RNA expression in pneumonia children, deep sequencing of small RNAs was performed in our study
The target genes were selected for further validation with Quantitative Real-Time PCR (qRT-PCR), and we found that the mRNA expression of 8 genes (PSMB5, ITGA6, MYCBP2, TCF7L2, UBE2V2, HIPK1, UBE2D2, and KANSL1) were downregulated in Adv-infected patients compared to healthy controls (Figure 5)
Summary
Human adenovirus (Adv) infection is responsible for most community-acquired pneumonia in infants and children [1, 2]. Adv causes infections for 5–10% of upper and lower respiratory tract infections in children, which results in pneumonia and nearly 1.3 million deaths of children every year [3, 4]. The fatality rates for untreated severe pneumonia or disseminated disease caused by Adv may even exceed to 50% [5, 6]. There are no efficacious antiviral drugs for Adv treatment until now. The traditional diagnosis of Adv infection is limited. To discover the interaction between the virus and its host will help us to find novel treatment and diagnosis for Adv infection
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