Lung epithelial cells resist influenza A infection by inducing the expression of cytochrome VI C oxidase that is regulated by hsa-miR-4276.
Othumpangat-S; Noti-J; Beezhold-D
FASEB J 2014 Apr; 28(1)(Suppl):1138.4
MicroRNAs regulate at least one third of all human genes and are phylogenetically well conserved. Influenza A virus infection induces several changes in host miRNA/protein profile and understanding the regulatory mechanism is essential for developing intervention approaches. In humans, mitochondrial energy metabolism involves mitochondrial respiration, electron transport and oxidative phosphorylation. Dysregulation of these processes has major pathological consequence and studies have shown that cytochrome oxidases are altered during viral infections. In these studies, influenza A infection of both human alveolar epithelial cells and human bronchial epithelial cells resulted in a significant down-regulation of hsa-miRNA-4276 (miRNA-4276). Influenza infection also triggered the overexpression of cytochrome oxidase VI C (COX6C). Transfection of epithelial cells with miRNA-4276 mimic reduced COX6C mRNA and protein expression. Similarly, epithelial cells transfected with miRNA4276 inhibitor increased COX6C mRNA and protein expression. Finally, transfection of cells with miRNA4276 inhibitor and subsequent infection with influenza A led to reduced influenza viral copy number. Taken together the data suggests that miRNA4276 is involved in the regulation of COX6C and that COX6C plays a role in resisting influenza A survival and propagation in lung epithelial cells. Thus, miRNA-4276 may be an important target in controlling the early stage infection of influenza A.
Ribonucleic-acids; Genes; Viral-diseases; Viral-infections; Respiratory-system-disorders; Respiratory-infections; Lung-cells; Cell-cultures; Cell-function; Cellular-reactions; Proteins; Host-resistance; Cell-metabolism; Cellular-transport-mechanism; Oxidative-phosphorylation; Cytopathology; Cell-alteration; Alveolar-cells; Cellular-respiration; Energy-metabolism; Humans
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