Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, P.R. China.
College of Animal Science and Technology, Guangxi University, Nanning, P.R. China.
Virulence. 2022 Dec;13(1):1407-1422. doi: 10.1080/21505594.2022.2112821.
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 (), during NDV infection via transcriptome analysis. To investigate the potential role of during NDV infection, we first confirmed the marked upregulation of in NDV-infected DF-1 or A549 cells through p53 and NF-κB pathways. Knockdown of 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 knockdown, indicating that propelled glutaminolysis for glutamate utilization and NDV replication in host cells. Taken together, our data identify that 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.
作为专性细胞内寄生虫，病毒完全依赖宿主代谢机制，并劫持宿主营养物质进行病毒复制。新城疫病毒（NDV）可引起急性、高度传染性的禽类疾病，并具有溶瘤作用。NDV 可在鸡和肿瘤细胞中高效复制。然而，NDV 如何为重编程宿主细胞代谢以实现其高效复制仍不清楚。我们之前通过转录组分析发现，NDV 感染过程中谷氨酸转运体基因 solute carrier family 1 member 3 () 显著上调。为了研究 在 NDV 感染过程中的潜在作用，我们首先通过 p53 和 NF-κB 通路证实了 在 NDV 感染的 DF-1 或 A549 细胞中明显上调。 下调抑制了 NDV 感染。Western blot 分析进一步证实，NDV 复制需要谷氨酰胺，而不是谷氨酸、天冬酰胺或天冬氨酸。代谢通量数据显示，NDV 促进了谷氨酰胺分解为三羧酸循环。重要的是， 通过 下调降低了谷氨酸和谷氨酸分解水平，表明 在宿主细胞中推动了谷氨酸分解以利用谷氨酸和 NDV 复制。总之，我们的数据表明 作为谷氨酰胺代谢的重要调节剂，在 NDV 感染过程中被 NDV 劫持以实现其高效复制。这些结果提高了我们对 NDV 与宿主细胞代谢相互作用的理解，并为进一步研究高效疫苗奠定了基础。
