Project description:The oncolytic potential of NDV has gained significant attention in the context of clinical trials. After systematically comparing the oncolytic activities of different NDV subtypes,we found that all subtypes, except for highly pathogenic genotype VII NDVs, display remarkable infectivity on tumor cell lines.A single amino acid mutation (F450L) in the NP protein at position 450 leads to an approximate 1000000-fold increase in the TCID50 value of genotype VII NDVs on tumor cells.Mechanistic inquiries unveiled that the amino acid at position 450 of the NP protein governs preferential translation of NDV mRNA.The preferential translation that regulates viral mRNA translation is often accompanied by modulation of the host translation machinery. Therefore, we established HeLa cell lines stably expressing NP protein from different NDV strains. Ribosome-bound mRNA was enriched to perform Ribosome Nascent-chain Complex sequencing(RNC-seq), while total cellular mRNA was enriched to conducted RNA-Seq . Untreated cells were used as controls. These experiments aimed to investigate the impact of NP on the host translation system.
Project description:Newcastle Disease Virus (NDV) is one of the most threatening viruses to the poultry industry, and it also exhibits oncolytic properties. In our research, we identified a non-oncolytic strain, genotype VII NDV strain I4, where the lack of oncolytic ability is attributed to its NP protein. To explore the mechanism of NP-mediated oncolysis by NDV, we focused on the differential interacting proteins of the NP proteins from two strains: the highly oncolytic Herts/33 strain and the poorly oncolytic I4 strain. The mass spectrometry results show the interacting protein profiles of the NP proteins from both virus strains. After infecting HeLa cells with each strain, we conducted immunoprecipitation using antibodies against the NP protein. Due to the lower expression of I4-associated proteins during replication, we further performed immunoprecipitation experiments using separately overexpressed NP proteins from I4 and Herts/33.
Project description:The NDV GM strain was used to infect DEF cells with 1moi, while an uninfected group was set up as a control. Changes in transcript levels of different genes after NDV infection of duck cells were identified by high-throughput sequencing. It is hoped to reveal the unique antiviral mechanism of waterfowl in resisting NDV infection.
Project description:To investigate the role of gene expression during Newcastle disease virus (NDV) infection.The NDV GM strain was used to infect DEF cells with 1moi, while an uninfected group was set up as a control.
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.
Project description:This project seeks to determine if there is a difference in expression between bladder cancer cells vs NDV-resistant bladder cancer cells.This result provides insight of the orchestrated transcriptomic changes that occur in the development and maintenance of NDV persistency of infection, which can be an useful resource for future downstream analysis of the identified targets.