Oligoadenylate synthetase-like (OASL) aggravated newcastle disease virus (NDV)-induced necroptosis in glioma cells

Newcastle disease virus (NDV) has emerged as an oncolytic agent in several cancers. Previous study has shown that NDV exerts cytolytic activity in glioma, however, the underlying mechanism has not been fully uncovered. Here the cytolytic activity of NDV in glioma and the associated mechanisms have been demonstrated. Infection with NDV inhibits cell proliferation and promotes cell apoptosis in LN229 cells. Further investigation showed that cytoplasmic organelle damage and cytoplasmic vacuolation were observed in LN229 cells after NDV infection. JC-1 staining assay proved that NDV caused cell apoptosis of LN229 cells by inducing mitochondrial dysfunction. We next speculated that NDV caused LN229 cells death through inducing necroptosis, but not ferroptosis, since the Fe2+ level did not alter after NDV infection. Furthermore, the NDV-caused cell death in LN229 cells was blocked by necroptosis inhibitor Nec1. Besides, RNA-seq analysis identified the different expression genes in NDV-infected LN229 cells. OASL, an antiviral gene, has been found to be directly induced by NDV infection. We also found that knockdown of OASL enhanced NDV infection-induced LN229 cells necroptosis. In summary, two aspects about cytolytic activity of NDV in glioma have been demonstrated. NDV presented cytolytic activity in glioma cells through inducing necroptosis. Additionally, targeting OASL may provide new strategy for enhancing necroptosis of glioma cells after NDV infection. Overall design: The normal group of LN299 was controlled with the infected group of NDV rLa Sota-GFP strain, and the molecular mechanism of necrotizing apoptosis of LN299 killed by NDV infection was investigated by using EdU cell proliferation, flow cytometry, transmission electron microscopy, JC-1 staining, Fe2+ detection, RNA isolation and sequencing, and cell transfection to observe the changes in genome and protein levels and activation of signaling pathways before and after infection at the cellular level and transcriptome gene level.