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

  • Exp Ther Med. 2021 Oct;22(4):1054. doi: 10.3892/etm.2021.10488.
Bing Han  1 Yizhong Wang  1  2 Mei Zheng  1  2
Affiliations
  • 1. Department of Pediatrics, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China.
  • 2. Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
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.

Keywords
apoptosis; autophagy; inflammatory cytokines; non-structural protein 1; respiratory syncytial virus.
Products