Inhibition of autophagy promotes human RSV NS1-induced inflammation and apoptosis in vitro.

Abstract

Human respiratory syncytial virus (RSV) is a major health challenge due to the lack of a safe and effective vaccine and antiviral drugs. RSV non-structural protein 1 (NS1) is the main inhibitor of antiviral signaling pathways in RSV infection; however, the underlying mechanism is unclear. The aim of the present study was to investigate of the role of NS1 and its relationship with autophagy. NS1-Flag plasmid was transfected into A549 cells and the levels of inflammatory cytokines, autophagy markers and apoptosis were detected. In addition, the cells were treated with an autophagy inhibitor, 3-methyladenine for 12 h prior to transfection with the NS1 plasmid to explore the role of autophagy in NS1-transfected cells. The results showed that the production of inflammatory cytokines and autophagy was induced in NS1-transfected cells, and indicated that autophagy prevents the production of cytokines and the activation of apoptosis. Furthermore, the results demonstrated that NS1 activated autophagy partly through the mTOR-p70 S6 kinase signaling pathway. The results suggest that autophagy induced by NS1 transfection through the mTOR pathway can hinder the production of inflammatory cytokines and interferon-α and inhibit cell apoptosis, which may help to explain why autophagy has been shown to be beneficial to viral replication in most studies.