Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
Virol Sin. 2021 Dec;36(6):1554-1565. doi: 10.1007/s12250-021-00445-0. Epub 2021 Sep 24.
Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway (PPP) flux and impaired oxidative phosphorylation (OXPHOS) in glucose utilization, and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis. These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism.
日本脑炎病毒（JEV）是亚洲流行地区病毒性脑炎的主要原因。JEV 的神经嗜性及其在神经元中的高效复制是发病机制的关键事件。揭示病毒与宿主细胞在代谢方面的相互作用对于阐明发病机制和提供新的抗病毒靶点都非常重要。本研究利用代谢组学和转录组学的整合分析，描绘了 JEV 感染早期神经元的代谢特征。糖酵解及其分支戊糖磷酸途径（PPP）通量增加，氧化磷酸化（OXPHOS）在葡萄糖利用中受损，以及脂质代谢的分解代谢模式被创造出来，以促进 JEV 复制所需前体的生物合成。神经元中糖酵解途径和 PPP 的药理学抑制表明其在维持 JEV 最佳传播中的不可或缺的作用。此外，代谢组学-转录组学调控网络的分析表明，脂质代谢在 JEV 感染过程中具有关键的生物学功能。几种促炎脂质代谢物显著上调，可能部分负责脑炎的进展。这些独特的代谢重编程特征可能使我们更深入地了解 JEV 感染的神经元，并为靶向代谢的有前途的抗病毒方法提供依据。
