Abstract
H1N1 swine influenza A virus (H1N1 SwIV) is one key subtype of influenza viruses with pandemic potential. MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression. MiRNAs relevant with H1N1 SwIV have rarely been reported. To understand the biological functions of miRNAs during H1N1 SwIV infection, this study profiled differentially expressed (DE) miRNAs in pulmonary alveolar macrophages from piglets during the H1N1 SwIV infection using a deep sequencing approach, which was validated by quantitative real-time PCR. Compared to control group, 70 and 16 DE miRNAs were respectively identified on post-infection day (PID) 4 and PID 7. 56 DE miRNAs were identified between PID 4 and PID 7. Our results suggest that most host miRNAs are down-regulated to defend the H1N1 SwIV infection during the acute phase of swine influenza whereas their expression levels gradually return to normal during the recovery phase to avoid the occurrence of too severe porcine lung damage. In addition, targets of DE miRNAs were also obtained, for which bioinformatics analyses were performed. Our results would be useful for investigating the functions and regulatory mechanisms of miRNAs in human influenza because pig serves as an excellent animal model to study the pathogenesis of human influenza.
Highlights
Integrative analysis of differentially expressed microRNAs of pulmonary alveolar macrophages from piglets during H1N1 swine influenza A virus infection
Our results suggest that most host miRNAs are down-regulated to defend the H1N1 SwIV infection during the acute phase of swine influenza whereas their expression levels gradually return to normal during the recovery phase to avoid the occurrence of too severe porcine lung damage
Recently, the impact of miRNAs expression on understanding molecular mechanisms in gene regulations has been remarkable because a single miRNA has the potential to target hundreds of distinct mRNA molecules and one mRNA molecule can be regulated by multiple miRNAs31, which means that miRNAs are attractive candidates as regulators of multiple pathways
Summary
Integrative analysis of differentially expressed microRNAs of pulmonary alveolar macrophages from piglets during H1N1 swine influenza A virus infection. As a short-lasting disease, swine influenza manifests itself with an incubation period of 1-3 days, the recovery phase follows, which is limited to 6 or 7 days after infection[8] This suggests that a large number of antiviral molecules may play a central role in the infection course, which has been partly proved by previous studies. During the acute phase of the disease, H1N1 SwIV induces an overwhelming and simultaneous pro-inflammatory cytokines in the lungs of infected pigs such as Th1, Th2, Th3, IFN-alpha, tumor necrosis factor-alpha, interwww.nature.com/scientificreports leukins, and so on[5,9,10]. Several have been demonstrated to be related with anti-viral functions or tissue damage at the acute stage of SwIV infection
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