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

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

PROVIDER: PRJNA947071 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23927217_1.fastq.gz	Fastqsanger.gz
	SRR23927217_2.fastq.gz	Fastqsanger.gz
	SRR23927218_1.fastq.gz	Fastqsanger.gz
	SRR23927218_2.fastq.gz	Fastqsanger.gz
	SRR23927219_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Project description:Newcastle disease (ND) affects a few hundred avian species including chicken, and the clinical outcome of Newcastle disease virus (NDV) infection ranges from mild to severe fatal disease depending on the NDV pathotype and the host species involved. Japanese quails serve as natural reservoirs of NDV and play important role in NDV epidemiology. While infection of chicken with velogenic NDV results in severe often fatal illness, the same infection in Japanese quails is results in in apparent infection. The molecular basis of this contrasting clinical outcomes of NDV infection is not yet known. We compared global gene expression in spleens of chicken and Japanese quails infected with a lentogenic or velogenic NDVs. We found contrasting regulation of key genes associated with NF-κB pathway and T-cell activation between chicken and Japanese quails. Our data suggests association of NDV resistance in Japanese quails to activation of NF-κB pathway and T cell proliferation.

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