SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism

As obligate intracellular parasites, viruses rely completely on host metabolic machinery and hijack host nutrients for viral replication. Newcastle disease virus (NDV) causes acute, highly contagious avian disease and functions as an oncolytic agent. NDV efficiently replicates in both chicken and tumour cells. However, how NDV reprograms host cellular metabolism for its efficient replication is still ill-defined. We previously identified a significantly upregulated glutamate transporter gene, solute carrier family 1 member 3 (<i>SLC1A3</i>), during NDV infection via transcriptome analysis. To investigate the potential role of <i>SLC1A3</i> during NDV infection, we first confirmed the marked upregulation of <i>SLC1A3</i> in NDV-infected DF-1 or A549 cells through p53 and NF-κB pathways. Knockdown of <i>SLC1A3</i> inhibited NDV infection. Western blot analysis further confirmed that glutamine, but not glutamate, asparagine, or aspartate, was required for NDV replication. Metabolic flux data showed that NDV promotes the decomposition of glutamine into the tricarboxylic acid cycle. Importantly, the level of glutamate and glutaminolysis were reduced by <i>SLC1A3</i> knockdown, indicating that <i>SLC1A3</i> propelled glutaminolysis for glutamate utilization and NDV replication in host cells. Taken together, our data identify that <i>SLC1A3</i> serves as an important regulator for glutamine metabolism and is hijacked by NDV for its efficient replication during NDV infection. These results improve our understanding of the interaction between NDV and host cellular metabolism and lay the foundation for further investigation of efficient vaccines.