Newcastle-disease-virus-induced ferroptosis through nutrient deprivation and ferritinophagy in tumor cells

Kan, Xianjin; Yin, Yuncong; Chen, Song; Tan, Lei; Qiu, Xusheng; Liao, Ying; Liu, Weiwei; Shao, Meng; Sun, Yingjie; Chen, Ding

doi:10.1016/j.isci.2021.102837

Cited by 51 publications

(54 citation statements)

References 59 publications

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“…Previous studies have shown that SARS-CoV-2 can induce these three kinds of programed cell death in susceptible epithelial cells and immune cells [23][24][25]. As for ferroptosis, whose morphological and biochemical features are distinct from PANoptosis, new castle virus (NDV) was the first virus to be discovered as a ferroptosis inducer in tumor cells [26]. NDV infection reduced the expression of Slc7a11 and Gpx4, resulting in the ferroptosis of infected cells.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

Xia

Zhang

You

2021

Viruses

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Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.

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Section: Introductionmentioning

confidence: 99%

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

Xia

Zhang

You

2021

Viruses

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“…Here, we showed for the first time that an oncolytic VV did not induce ferroptosis in cancer cells. However, another type of OV, Newcastle-disease virus, can induce ferroptosis in infected tumor cells [ 48 ]. It is interesting to note that ferroptosis and apoptosis can interact through certain signaling pathways, and inducers for apoptosis and ferroptosis may lead to improved tumoricidal efficacy [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Chen

Zhu

et al. 2022

Biomedicines

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Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides. In this study, we explore the combination of a ferroptosis activator with an oncolytic vaccinia virus in tumor models. Erastin induced cell death in hepatoma, colon, and ovarian cancer cells, but not in melanoma cancer cells. Erastin, not the oncolytic vaccinia virus (OVV), induced the expression of key marker genes for ferroptosis in cancer cells. In hepatocellular carcinoma and colon cancer models, either erastin or OVV inhibited tumor growth, but a combination of the two yielded the best therapeutic effects, as indicated by inhibited tumor growth or regression and longer host survival. Immunological analyses indicate that erastin alone had little or no effect on systemic immunity or local immunity in the tumor. However, when combined with OV, erastin enhanced the number of activated dendritic cells and the activity of tumor-infiltrating T lymphocytes as indicated by an increase in IFN-γ+CD8+ and PD-1+CD8+ T cells. These results demonstrate that erastin can exert cytotoxicity on cancer cells via ferroptosis, but has little effect on immune activity by itself. However, when combined with an OVV, erastin promoted antitumoral immunity and efficacy by increasing the number of activated dendritic cells and promoting the activities of tumor specific CD8+ T cells in the tumor.

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“…The morphological hallmarks of NDV-induced apoptosis, as visualized by confocal microscopy images of infected HeLa cells, were: (i) active apoptosis with cellular shrinkage and DNA fragmentation, (ii) advanced apoptosis displaying extensive membrane blebbing, and (iii) late apoptosis showing apoptotic bodies [54]. NDV induces multimodal cell death responses according to programmed cell death, including apoptosis [37], autophagic cell death [44], necroptosis [37], pyroptosis [55], and ferroptosis [56].…”

Section: Tumor-selective Oncolysis: Intrinsic Signaling Pathwaysmentioning

confidence: 99%

“…Another way to break resistance to apoptosis is to use a different way of programmed cell death. Ferroptosis is a new form of programmed cell death that is induced by NDV [56]. It involves the activation of p53 [79], downregulation of extracellular cystine uptake by xCantiporter [80], and iron-dependent accumulation of reactive oxygen species (ROS), leading to lethal levels of phospholipid peroxides.…”

Section: Breaking Cancer Therapy Resistanciesmentioning

confidence: 99%

“…It involves the activation of p53 [79], downregulation of extracellular cystine uptake by xCantiporter [80], and iron-dependent accumulation of reactive oxygen species (ROS), leading to lethal levels of phospholipid peroxides. The recent study suggests that the p53-SLC7A11-PGX4 axis plays a central role in inducing ferroptosis, leading to a new form of NDV-induced cancer cell death [56]. (iv) The breaking of resistance to hypoxia.…”

Section: Breaking Cancer Therapy Resistanciesmentioning

confidence: 99%

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Molecular Mechanisms of Anti-Neoplastic and Immune Stimulatory Properties of Oncolytic Newcastle Disease Virus

Schirrmacher¹

2022

Biomedicines

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Oncolytic viruses represent interesting anti-cancer agents with high tumor selectivity and immune stimulatory potential. The present review provides an update of the molecular mechanisms of the anti-neoplastic and immune stimulatory properties of the avian paramyxovirus, Newcastle Disease Virus (NDV). The anti-neoplastic activities of NDV include (i) the endocytic targeting of the GTPase Rac1 in Ras-transformed human tumorigenic cells; (ii) the switch from cellular protein to viral protein synthesis and the induction of autophagy mediated by viral nucleoprotein NP; (iii) the virus replication mediated by viral RNA polymerase (large protein (L), associated with phosphoprotein (P)); (iv) the facilitation of NDV spread in tumors via the membrane budding of the virus progeny with the help of matrix protein (M) and fusion protein (F); and (v) the oncolysis via apoptosis, necroptosis, pyroptosis, or ferroptosis associated with immunogenic cell death. A special property of this oncolytic virus consists of its potential for breaking therapy resistance in human cancer cells. Eight examples of this important property are presented and explained. In healthy human cells, NDV infection activates the RIG-MAVs immune signaling pathway and establishes an anti-viral state based on a strong and uninhibited interferon α,ß response. The review also describes the molecular determinants and mechanisms of the NDV-mediated immune stimulatory effects, in which the viral hemagglutinin-neuraminidase (HN) protein plays a prominent role. The six viral proteins provide oncolytic NDV with a special profile in the treatment of cancer.

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Newcastle-disease-virus-induced ferroptosis through nutrient deprivation and ferritinophagy in tumor cells

Cited by 51 publications

References 59 publications

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Molecular Mechanisms of Anti-Neoplastic and Immune Stimulatory Properties of Oncolytic Newcastle Disease Virus

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