Glutamine is required for red-spotted grouper nervous necrosis virus replication via replenishing the tricarboxylic acid cycle
Glutamine is required for red-spotted grouper nervous necrosis virus replication via replenishing the tricarboxylic acid cycle
复制标题
红斑石斑鱼神经坏死病毒通过补充三羧酸循环进行复制需要谷氨酰胺。
DOI：
10.1016/j.virusres.2016.11.007
复制
发表时间：
2017-01-02
期刊：
影响因子：
5
通讯作者：
Lin, Li
中科院分区：
文献类型：
--
作者：
Asim, Muhammad;Jiang, Sanjie;Lin, Li
谷氨酰胺是重要的营养素之一，在碳代谢途径中起着重要作用，并且已被报道是多种人类DNA病毒复制所必需的。然而，谷氨酰胺是否是RNA病毒复制所必需的以及相关的机制仍然是难以捉摸的。神经坏死病毒（Nervous Necrosis Virus，NNV）是一种正链RNA病毒，可感染许多重要的水生生物，给世界水产养殖业造成巨大的经济损失。研究了谷氨酰胺对石斑鱼神经坏死病毒（RGNNV）复制的影响。结果表明，谷氨酰胺的缺乏不影响细胞活力，但显着抑制RGNNV复制，表明谷氨酰胺是RGNNV复制所必需的。谷氨酰胺可以通过谷氨酰胺酶（GLS）转化为α-酮戊二酸（α-KG）以加入三羧酸（TCA）循环。通过GLS抑制剂：双-2-5-苯乙酰氨基-1，3，4-噻二唑-2-乙基硫醚（BPTES）抑制GLS的活性可显著抑制RGNNV复制，而添加TCA循环中间体：α-KG、草酰乙酸（OAA）或丙酮酸盐可显著恢复无谷氨酰胺培养基中的RGNNV复制，表明RGNNV复制需要谷氨酰胺是由于补充TCA循环。综上所述，谷氨酰胺可以通过TCA循环调控RGNNV的复制，这为今后RGNNV的防治提供了新的思路。(C)2016爱思唯尔B. V.保留所有权利。
Glutamine, one of the most important nutrients, plays a vital role in carbon metabolic pathway and has been reported to be required for the replication of several human DNA viruses. However, whether glutamine is required for RNA virus replication and the related mechanism remains elusive. Nervous necrosis virus (NNV), a positive-stranded RNA virus, can infect a number of important aquatic species and has caused great economic losses in aquaculture industry worldwide. In this study, the effects of glutamine on red-spotted grouper nervous necrosis virus (RGNNV) replication were investigated. The results showed that lack of glutamine did not affect the cell viability, but dramatically inhibited RGNNV replication, indicating that glutamine was required for RGNNV replication. Glutamine can be converted to a-ketoglutarate (alpha-KG) by glutaminase (GLS) to join in the tricarboxylic acid (TCA) cycle. Inhibiting the activity of GLS by a GLS inhibitor: bis-2-5-phenylacetamido-1,3,4-thiadiazol-2-ethyl sulfide (BPTES) significantly inhibited RGNNV replication, while adding the TCA cycle intermediates: alpha-KG, oxaloacetic acid (OAA), or pyruvate significantly restored RGNNV replication in glutamine-free medium, indicating that the requirement of glutamine for RGNNV replication was due to replenishing the TCA cycle. Taken together, these data revealed that glutamine could regulate RGNNV replication via TCA cycle, which will pave a new way for the prevention of the RGNNV infection in the future. (C) 2016 Elsevier B.V. All rights reserved.