HIV-1 replication and latency are balanced by mTOR-driven cell metabolism.
HIV-1 replication and latency are balanced by mTOR-driven cell metabolism.
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DOI：
10.3389/fcimb.2022.1068436
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发表时间：
2022
影响因子：
5.7
通讯作者：
Furler O'Brien RL
中科院分区：
文献类型：
--
作者：
Crater JM;Nixon DF;Furler O'Brien RL
人类免疫缺陷病毒1型（HIV-1）在病毒复制的各个方面都依赖于宿主细胞代谢。有效的HIV-1进入、逆转录和整合发生在活化的T细胞中，因为HIV-1蛋白会选择宿主代谢途径，为病毒粒子产生的合成代谢需求提供燃料。HIV-1病毒的生命周期特别依赖于mTOR，它驱动病毒进入、复制和潜伏期所需的信号传导和代谢途径。作为宿主细胞代谢的中枢调节剂，mTOR及其下游效应物有助于调节糖酵解和戊糖磷酸途径中酶的表达，以及调节氨基酸摄取、脂质代谢和自噬的其他代谢途径。在HIV-1发病机制中，mTOR与HIF-1α和Myc信号通路一起改变宿主细胞代谢，为病毒复制创造最佳环境。在病毒生命周期的早期阶段需要增加糖酵解和戊糖磷酸途径的活性，例如为逆转录提供足够的dNTPs。在后期阶段，脂肪酸合成是产生病毒出芽所需的胆固醇和膜脂所必需的。由代谢和mTOR信号驱动的原病毒的表观遗传学同样控制着活动性和潜伏性感染。乙酰辅酶a和甲基丰度，分别由TCA循环和氨基酸摄取提供，可能调节潜伏感染和再激活。因此，理解和探索细胞代谢与HIV-1发病机制之间的新联系可能会对潜伏病毒储存库产生新的见解，并为新的治疗和治愈策略提供动力。
Human Immunodeficiency virus type 1 (HIV-1) relies on host cell metabolism for all aspects of viral replication. Efficient HIV-1 entry, reverse transcription, and integration occurs in activated T cells because HIV-1 proteins co-opt host metabolic pathways to fuel the anabolic requirements of virion production. The HIV-1 viral life cycle is especially dependent on mTOR, which drives signaling and metabolic pathways required for viral entry, replication, and latency. As a central regulator of host cell metabolism, mTOR and its downstream effectors help to regulate the expression of enzymes within the glycolytic and pentose phosphate pathways along with other metabolic pathways regulating amino acid uptake, lipid metabolism, and autophagy. In HIV-1 pathogenesis, mTOR, in addition to HIF-1α and Myc signaling pathways, alter host cell metabolism to create an optimal environment for viral replication. Increased glycolysis and pentose phosphate pathway activity are required in the early stages of the viral life cycle, such as providing sufficient dNTPs for reverse transcription. In later stages, fatty acid synthesis is required for creating cholesterol and membrane lipids required for viral budding. Epigenetics of the provirus fueled by metabolism and mTOR signaling likewise controls active and latent infection. Acetyl-CoA and methyl group abundance, supplied by the TCA cycle and amino acid uptake respectively, may regulate latent infection and reactivation. Thus, understanding and exploring new connections between cellular metabolism and HIV-1 pathogenesis may yield new insights into the latent viral reservoirs and fuel novel treatments and cure strategies.
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影响因子：
1.5
作者：
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影响因子：
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影响因子：
6.4
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影响因子：
6.4
作者：
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通讯作者：
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