Highlights Oncolytic viruses NDV caused tumor cells death through ferroptosis NDV-induced ferroptosis acts through nutrient deprivation by suppression of System Xc À P53 activation is required for NDV-induced ferroptosis initiation Ferritinophagy induced by NDV promotes ferroptosis through release of ferrous iron

Autophagy is a process of degradation to maintain cellular homeostatic by lysosomes, which ensures cellular survival under various stress conditions, including nutrient deficiency, hypoxia, high temperature, and pathogenic infection. Xenophagy, a form of selective autophagy, serves as a defense mechanism against multiple intracellular pathogen types, such as viruses, bacteria, and parasites. Recent years have seen a growing list of animal viruses with autophagy machinery. Although the relationship between autophagy and human viruses has been widely summarized, little attention has been paid to the role of this cellular function in the veterinary field, especially today, with the growth of serious zoonotic diseases. The mechanisms of the same virus inducing autophagy in different species, or different viruses inducing autophagy in the same species have not been clarified. In this review, we examine the role of autophagy in important animal viral infectious diseases and discuss the regulation mechanisms of different animal viruses to provide a potential theoretical basis for therapeutic strategies, such as targets of new vaccine development or drugs, to improve industrial production in farming.

SummaryA number of new cell death processes have been discovered in recent years, including ferroptosis, which is characterized by the accumulation of lipid peroxidation products derived from iron metabolism. The evidence suggests that ferroptosis has a tumor-suppressor function. However, the mechanism by which ferroptosis mediates the response of tumor cells to oncolytic viruses remains poorly understood. Newcastle disease virus can selectively replicate in tumor cells. We show that NDV-induced ferroptosis acts through p53-SLC7A11-GPX4 pathway. The expression of tumor suppressor gene p53 increased after NDV infection, and the expressions of SLC7A11 and SLC3A2 were down-regulated, leading to the inhibition of glutathione synthesis and a decrease in glutathione peroxidase 4 expression. The chemical compound erastin, which induces ferroptosis, also down-regulated glutathione synthase expression and caused lipid peroxide accumulation and cell death. Meanwhile, the levels of intracellular reactive oxygen species and lipid peroxides increased in tumor cells. Ferritinophagy was induced by NDV promotion of ferroptosis through the release of ferrous iron and an enhanced Fenton reaction. Collectively, these observations demonstrated that NDV can kill tumor cells through ferroptosis. Our study provides novel insights into the mechanisms of NDV-induced ferroptosis and highlights the critical role of viruses in treating therapy-resistant cancers.

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