Influenza virus non‑structural protein 1 inhibits the production of interferon β of alveolar epithelial cells upon the infection of influenza A H1N1.

Influenza A affects a large population worldwide. Influenza virus evades immune responses via various mechanisms, including through the modification of the immune microenvironment. Influenza virus non-structural protein 1 (NS1) encoded by the virus genome inhibits type I interferon (IFN) signaling pathways, which is essential for viral clearance. However, the precise mechanisms of NS1-mediated immune suppression remain poorly understood. The results of the present study demonstrated that mice infected with NS1-expressing influenza A H1N1 virus had lower expression levels of IFN beta in the lung. In addition, it was revealed that the human alveolar epithelial A549 cell line infected with influenza virus A H1N1 produced antiviral IFN beta. The production of IFN beta during infection was demonstrated to be a self-dependent autocrine process. A549 cells transfected with H1N1 NS1 lost the ability to produce IFN beta upon H1N1 infection or IFN beta stimulation. NS1 inhibited the expression of IFN receptors. Furthermore, NS1 inhibited the activation of signal transducers and activators of transcription (STAT) 1 and STAT2, as well as the consequent IFN beta production. These data indicate that NS1 serves an important role during virus evasion by affecting the production of IFN beta via multiple mechanisms.