Interferon-stimulated gene products as regulators of central carbon metabolism.
Interferon-stimulated gene products as regulators of central carbon metabolism.
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干扰素刺激的基因产物作为中心碳代谢的调节剂。
DOI：
10.1111/febs.15625
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
McCullagh JSO
中科院分区：
文献类型：
--
作者：
Ebrahimi KH;Gilbert-Jaramillo J;James WS;McCullagh JSO
ISG产品被认为直接阻断病毒复制。我们提出了一个替代机制的基础上出现的证据。我们讨论了两种ISG蛋白的代谢产物，即RSAD 2和NOS，抑制GAPDH的活性以调节中心碳代谢，并通过至少四种机制支持广谱抗病毒免疫应答：类花生酸风暴，通过MHC-I的抗原交叉呈递，调节NFAT和NF-κB途径，以及病毒蛋白的S-亚硝基化。 为了应对病毒感染，先天免疫系统迅速激活几种干扰素刺激基因（ISG）的表达，其蛋白质和代谢产物被认为直接干扰病毒的生命周期。在这里，我们认为ISG的两种特定蛋白质产物进行的生化反应调节中心碳代谢，以支持广谱抗病毒反应。我们证明，由金属酶一氧化氮合酶和自由基S-腺苷甲硫氨酸（SAM）酶RSAD 2产生的代谢产物抑制管家和糖酵解酶甘油醛3-磷酸脱氢酶（GAPDH）的活性。我们讨论了这种抑制可能会刺激一系列代谢和信号传导过程，以支持广谱免疫反应。基于这些分析，我们提出，在细胞先天免疫反应恶化的个体（如老年人）中抑制GAPDH可能有助于治疗病毒性疾病，如COVID-19。
ISG products are believed to directly block viral replication. We propose an alternative mechanism based on emerging evidence. We discuss that the metabolic products of two ISG proteins, namely RSAD2 and NOS, inhibit activity of GAPDH to regulate central carbon metabolism and support a broad‐spectrum antiviral immune response via at least four mechanisms: eicosanoids storm, antigen cross‐presentation via MHC‐I, modulating NFAT and NF‐κB pathways, and S‐nitrosylation of viral proteins. In response to viral infections, the innate immune system rapidly activates expression of several interferon‐stimulated genes (ISGs), whose protein and metabolic products are believed to directly interfere with the viral life cycle. Here, we argue that biochemical reactions performed by two specific protein products of ISGs modulate central carbon metabolism to support a broad‐spectrum antiviral response. We demonstrate that the metabolites generated by metalloenzymes nitric oxide synthase and the radical S‐adenosylmethionine (SAM) enzyme RSAD2 inhibit the activity of the housekeeping and glycolytic enzyme glyceraldehyde 3‐phosphate dehydrogenase (GAPDH). We discuss that this inhibition is likely to stimulate a range of metabolic and signalling processes to support a broad‐spectrum immune response. Based on these analyses, we propose that inhibiting GAPDH in individuals with deteriorated cellular innate immune response like elderly might help in treating viral diseases such as COVID‐19.
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影响因子：
3.7
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影响因子：
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通讯作者：
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