Abstract
BackgroundAvian influenza remains a serious threat to human health. The consequence of human infection varies markedly among different subtypes of avian influenza viruses. In addition to viral factors, the difference in host cellular response is likely to play a critical role. This study aims at elucidating how avian influenza infection perturbs the host’s miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach.ResultsThe results showed that dysregulation of miRNA expression was mainly observed in highly pathogenic avian influenza A H5N1 infection. We found that miR-21*, miR-100*, miR-141, miR-574-3p, miR-1274a and miR1274b were differentially expressed in response to influenza A virus infection. Interestingly, we demonstrated that miR-141, which was more highly induced by H5N1 than by H1N1 (p < 0.05), had an ability to suppress the expression of a cytokine - transforming growth factor (TGF)-β2. This was supported by the observation that the inhibitory effect could be reversed by antagomiR-141.ConclusionsSince TGF-β2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza H1N1 (but not the other avian influenza subtypes) could induce a persistent expression of TGF-β2, we speculate that the modulation of TGF-β2 expression by different influenza subtypes via miR-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression.
Highlights
Avian influenza remains a serious threat to human health
Differential miRNA expression in H5N1 and H1N1 influenza virus infected cells The cell line - NCI-H292, infected with various preparations of influenza viruses was analysed for miRNA expression profiles subsequently
In this study we examined the connection between influenza A virus infection and the global patterns of cellular miRNA expression
Summary
Avian influenza remains a serious threat to human health. This study aims at elucidating how avian influenza infection perturbs the host’s miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach. Avian influenza remains a serious threat to poultry and human health. While it has been well documented that infection with H5N1 results in high mortality in humans [2,3,4,5], the cellular pathway leading to such adverse outcome is unknown. Cytokine storm and reactive haemophagocytic syndrome are the key features that distinguish H5N1 infection from severe seasonal influenza. These indirect mechanisms seem to play an even more important role than direct cell killing due to lytic viral infection
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