Oncolytic viruses selectively infect and kill tumor cells, but the metabolic adaptations that support their replication remain incompletely understood. Here, using oncolytic Newcastle disease virus (NDV) as a model, we identify glutamic-oxaloacetic transaminase 1 (GOT1) as a key metabolic enzyme required for efficient viral replication through its dual role in de novo pyrimidine synthesis. In NDV-infected tumor cells, GOT1 promotes aspartate production through the malate-aspartate shuttle to support pyrimidine biosynthesis, while also maintaining NAD + /NADH homeostasis to activate the mTOR-S6K-CAD signaling axis and further enhance pyrimidine synthesis. These GOT1-dependent metabolic and signaling adaptations sustain pyrimidine biosynthesis and viral replication. In addition, NDV infection promotes pyrimidinosome assembly, and GOT1 functions as a pyrimidinosome-associated component. Together, these findings reveal a mechanism by which oncolytic NDV rewires host pyrimidine metabolism to support its replication and provide a rationale for metabolic modulation of oncolytic virotherapy.
Tang et al. (Wed,) studied this question.