Control of viral latency in neurons by axonal mTOR signaling and the 4E-BP translation repressor
Control of viral latency in neurons by axonal mTOR signaling and the 4E-BP translation repressor
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DOI：
10.1101/gad.190157.112
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发表时间：
2012-07-15
影响因子：
10.5
通讯作者：
Mohr, Ian
中科院分区：
文献类型：
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作者：
Kobayashi, Mariko;Wilson, Angus C.;Mohr, Ian
潜伏性单纯疱疹病毒-1（HSV 1）基因组在外周神经节周期性地重新激活，启动生产性复制所需的基因表达程序。轴突检测到的分子线索是否可以传递到细胞体，并被利用来调节神经元核中潜在的基因组表达，这是未知的。使用神经元培养模型，我们发现抑制mTOR，耗尽其调节亚基raptor，或诱导缺氧都触发再激活。虽然持续的mTORC 1激活抑制再激活，突变的4 E-BP（eIF 4 E结合蛋白）翻译阻遏物不响应mTORC 1刺激再激活。最后，抑制轴突中的mTOR诱导再激活。因此，控制翻译的轴突mTOR信号传导的局部变化在空间隔离的隔室中调节潜伏的HSV 1基因组。
Latent herpes simplex virus-1 (HSV1) genomes in peripheral nerve ganglia periodically reactivate, initiating a gene expression program required for productive replication. Whether molecular cues detected by axons can be relayed to cell bodies and harnessed to regulate latent genome expression in neuronal nuclei is unknown. Using a neuron culture model, we found that inhibiting mTOR, depleting its regulatory subunit raptor, or inducing hypoxia all trigger reactivation. While persistent mTORC1 activation suppressed reactivation, a mutant 4E-BP (eIF4E-binding protein) translational repressor unresponsive to mTORC1 stimulated reactivation. Finally, inhibiting mTOR in axons induced reactivation. Thus, local changes in axonal mTOR signaling that control translation regulate latent HSV1 genomes in a spatially segregated compartment.