数字农科院2.0

p53-mediated regulation of electron transport chain and nucleotide synthesis during Newcastle disease virus infection

文献类型： 外文期刊

作者： Zhao, Changrun;Tang, Ning;Wang, Jing;Qu, Yang;Tan, Lei;Song, Cuiping;Qiu, Xusheng;Liao, Ying;Luo, Tingrong;Ding, Chan;Sun, Yingjie

作者机构：

关键词： NDV;mitochondrial metabolism;electron transport chain;p53;reactive oxygen species;nucleotide synthesis

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Mitochondria and their electron transport chain (ETC) constitute the central machinery for cellular energy metabolism and biosynthetic regulation. Disruption of the ETC leads to reactive oxygen species (ROS) production and metabolic imbalance, but its precise role in viral replication and infection remains to be elucidated. In this study, we used Newcastle disease virus (NDV), an important avian pathogen and a promising oncolytic virus, as a model to explore its relationship with cellular mitochondrial metabolism. We demonstrate that NDV infection induces varying degrees of mitochondrial fragmentation, membrane potential dissipation, and ROS production, especially in p53-null H1299 cells compared to p53-wild-type A549 cells. ETC impairment restricts NDV replication primarily by limiting aspartate and pyrimidine nucleotide biosynthesis, rather than through ROS-mediated cytotoxicity or energy depletion. Notably, NDV replication in p53-null cells is highly sensitive to ETC complexes I and III inhibition, which can be rescued by exogenous aspartate or uridine supplementation. Mechanistically, p53 serves as a metabolic buffer, protecting mitochondrial function and maintaining precursor availability during viral infection. These findings elucidate the selective and differential utilization of mitochondrial ETC components by NDV and reveal that p53 status shapes cellular susceptibility to NDV-induced metabolic stress. Our work highlights mitochondrial metabolism and p53 as potential targets for antiviral and oncolytic strategies against NDV.IMPORTANCEThis study uncovers the intricate relationship between Newcastle disease virus (NDV) infection and host cell mitochondrial metabolism, with a particular emphasis on the pivotal regulatory role of p53. As both an important avian pathogen and a promising oncolytic virus, NDV disrupts mitochondrial function and the electron transport chain, leading to p53-mediated alterations in cellular energy metabolism and redox homeostasis. Our findings not only deepen the understanding of NDV-mitochondria interactions but also highlight the central role of p53 in viral infection and oncolytic mechanisms. These insights provide a theoretical foundation and novel therapeutic targets for antiviral and anticancer strategies based on p53 or mitochondrial pathways.

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