Recently, SHVRI of CAAS revealed the key interaction between Newcastle disease virus (NDV) and host mitochondrial metabolism, as well as the "guardian" role played by the tumor suppressor gene p53 in this process. The related findings were published in the Journal of Virology.

Background

NDV is not only a pathogen threatening the poultry industry but also regarded as a promising oncolytic virus due to its selective targeting of tumor cells. Mitochondria, beyond their role in energy supply, play a central role in metabolic regulation, ion homeostasis, and oxidative stress. Changes in mitochondrial function can profoundly influence viral replication efficiency and pathogenicity.

Findings

Studies have revealed that the mitochondrial electron transport chain (ETC) supports NDV replication primarily by providing aspartate and precursors for pyrimidine nucleotide synthesis. Notably, the sensitivity of different cells to NDV is closely associated with the presence of the p53. Mechanistically, p53 acts as a metabolic buffer or "guardian" during infection, maintaining mitochondrial stability. This process is exploited by the virus to stabilize the supply of metabolic precursors required for its replication. This research offers new insights into enhancing the oncolytic efficacy and safety of NDV by regulating mitochondrial metabolism and the p53 pathway. It also establishes a theoretical foundation for precise strategies in oncolytic virotherapy.

p53 protects mitochondria through metabolic buffering and influences the infection process of NDV

Zhao Changrun, a Ph.D. candidate enrolled in the collaborative training program between Guangxi University and SHVRI, and Tang Ning, a postdoctoral fellow at SHVRI served as co-first authors of the paper. The corresponding authors were Prof. Chan Ding, Yingjie Sun, and Tingrong Luo. This research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.

       Link to the original article

https://journals.asm.org/doi/10.1128/jvi.01576-25