The mitochondrial transaminase GOT2 supports Japanese encephalitis virus replication in neuronal cells

Japanese encephalitis virus (JEV), the primary cause of viral encephalitis in Asia, does not currently have known antiviral therapies. Researchers have now uncovered a metabolic pathway involved in JEV replication within neuronal cells. Utilizing time-resolved transcriptomics and proteomics, they discovered that JEV infection led to the upregulation of interferon-stimulated proteins and alterations in enzymes responsible for central carbon and energy metabolism, including the tricarboxylic acid cycle, glycolysis, oxidative phosphorylation, and glutaminolysis.

The team found that oxidative phosphorylation remodeling was interconnected with glutamine metabolism, suggesting a dependence on this process. Further experiments showed that inhibiting glutamine metabolism using DON reduced JEV RNA, viral proteins, and infectious virus production. In contrast, glycolytic inhibition and AKT modulation did not show significant effects.

Additionally, silencing the mitochondrial transaminase GOT2 also decreased JEV RNA, viral protein, and infectious virus generation in human SH-SY5Y cells. These findings identify a potential metabolic axis involving glutamine and GOT2 as a key dependency for JEV replication and propose a promising candidate for host-directed antiviral therapies.