Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication.
Metabolomics Exploration of Pseudorabies Virus Reprogramming Metabolic Profiles of PK-15 Cells to Enhance Viral Replication.
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伪狂犬病病毒重编程 PK-15 细胞代谢谱以增强病毒复制的代谢组学探索
DOI：
10.3389/fcimb.2020.599087
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发表时间：
2020
影响因子：
5.7
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Gou H;Bian Z;Li Y;Cai R;Jiang Z;Song S;Zhang K;Chu P;Yang D;Li C
对于在宿主细胞中发生的病毒复制，低分子量代谢物是病毒体组装所必需的。近年来，代谢组学在揭示病毒与宿主相互作用的高度复杂机制方面显示出巨大的潜力。本研究采用气相色谱-质谱（GC-MS）联用技术研究了伪狂犬病病毒（PRV）强毒株和经典弱毒株感染PK-15细胞后的代谢网络。虽然总的代谢物的数量，其水平被改变的变异强毒株或经典的减毒株感染后8和16小时感染（hpi）是不同的，预测水平的差异代谢成分被证明是与特定的途径，包括糖酵解以及氨基酸和核苷酸代谢。葡萄糖耗竭和糖酵解抑制剂2DG和草胺酸可降低PRV在PK-15细胞中的复制水平。此外，抑制戊糖磷酸途径（PPP）导致病毒滴度明显下降，但阻止三羧酸（TCA）循环中的氧化磷酸化对病毒复制的影响极小。谷氨酰胺饥饿导致病毒滴度下降，这可以通过在培养基中补充添加来恢复。然而，抑制谷氨酰胺酶（GLS）活性或2-酮戊二酸补充到谷氨酰胺缺失的DMEM中并没有改变PK-15细胞中PRV的复制。目前的研究结果表明，PRV重新编程PK-15细胞的代谢活性。糖酵解、PPP和谷氨酰胺代谢到核苷酸合成的代谢流是PRV增强其复制所必需的。这项研究将有助于确定PRV在宿主细胞中复制所利用的生物化学物质，这些知识可以帮助开发新的抗病毒策略。
For viral replication to occur in host cells, low-molecular-weight metabolites are necessary for virion assembly. Recently, metabolomics has shown great promise in uncovering the highly complex mechanisms associated with virus-host interactions. In this study, the metabolic networks in PK-15 cells infected with a variant virulent or classical attenuated pseudorabies virus (PRV) strains were explored using gas chromatography-mass spectrometry (GC-MS) analysis. Although total numbers of metabolites whose levels were altered by infection with the variant virulent strain or the classical attenuated strain were different at 8 and 16 h post infection (hpi), the predicted levels of differential metabolic components were shown to be associated with specific pathways, including glycolysis as well as amino acid and nucleotide metabolism. The glucose depletion and glycolysis inhibitors 2DG and oxamate could reduce the level of PRV replication in PK-15 cells. In addition, the inhibition of the pentose phosphate pathway (PPP) resulted in an obvious decline of viral titers, but the prevention of oxidative phosphorylation in the tricarboxylic acid (TCA) cycle had a minimal effect on viral replication. Glutamine starvation resulted in the decline of viral titers, which could be restored by supplemental addition in the culture media. However, inhibition of glutaminase (GLS) activity or the supplement of 2-ketoglutarate into glutamine-deleted DMEM did not alter PRV replication in PK-15 cells. The results of the current study indicate that PRV reprograms the metabolic activities of PK-15 cells. The metabolic flux from glycolysis, PPP and glutamine metabolism to nucleotide biosynthesis was essential for PRV to enhance its replication. This study will help to identify the biochemical materials utilized by PRV replication in host cells, and this knowledge can aid in developing new antiviral strategies.
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影响因子：
5.2
作者：
Gou H;Zhao M;Yuan J;Xu H;Ding H;Chen J
通讯作者：
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影响因子：
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通讯作者：
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4.8
作者：
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通讯作者：
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