Abstract
The extent of lung injury in influenza A infections may be due to innate deficient responses. A severe respiratory disease leads to acute respiratory distress syndrome where viral replication occurs in the epithelial cells (AECs) lining the alveolus. It was suggested that influenza non-structural-1A binding protein (NS1A) in AECs plays a key role in viral maintenance by preventing transcriptional induction of antiviral interferons. On the other hand, NS1A physically interacts with the aryl hydrocarbon receptor (AhR). AhR is a dioxin-activated transcription factor that mediates the toxic effects via cytosolic dioxin:AhR dimerization with nuclear translocator Arnt, resulting in binding to dioxin response element (DRE) of sensitive genes. Here, SITECON, an established computational tool for transcriptional factor binding site recognition, was used to quantify DREs in promoter area of genes encoding NS1A, AhR and Arnt. It was shown that these genes possess, respectively, 2, 4 and 5 potentially active DREs (core nucleotide sequence 3' A-CGCAC 5') in their enhancer regions. Also, Western blot analysis of lysates of confluent human epithelial cells (line A549) pretreated with 10 ppt dioxin for 36 h revealed a 5.8-fold increase of NS1A-specific polypeptide. So, it was suggested that pulmonary concentration of dioxin upregulating NS1A via AhR/Arnt signaling pathway should be slightly above current dioxin levels in general population (~ 4 ppt). Data obtained correspond to population studies in some regions of Vietnam, where elevated concentrations of dioxin served as a promotional factor for lung injury during seasonal influenza A outbreaks.
- Copyright ©the authors 2017