Establishing a Herpesvirus Quiescent Infection in Differentiated Human Dorsal Root Ganglion Neuronal Cell Line Mediated by Micro-RNA Overexpression.

Establishing a Herpesvirus Quiescent Infection in Differentiated Human Dorsal Root Ganglion Neuronal Cell Line Mediated by Micro-RNA Overexpression.
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DOI:
10.3390/pathogens11070803
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发表时间:
2022-07-16
期刊:
Pathogens (Basel, Switzerland)
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其他
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1型单纯疱疹病毒是一种嗜神经型病原体,与严重脑炎、口面部疼痛感和其他慢性神经性并发症相关。急性感染后,病毒可在三叉神经节(TG)及其他感觉神经节和自主神经节,包括背根神经节(DRG)等神经元中建立终身潜伏期。这种再激活是由各种生理或情绪压力周期性地发生的。我们一直在开发人类DRG神经元细胞培养模型HD10.6,该模型模拟成熟神经元的潜伏期和再激活,具有强大的神经元生理学。我们发现,在不使用无环鸟苷(ACV)的情况下,miR124过表达可以使病毒保持静止感染,并积累潜伏相关转录物(LAT)。另一方面,即刻早期(IE)基因ICP0极低,潜伏病毒经曲古霉素A (TSA)处理后可被重新激活。总之,这些观察结果表明,microRNA在促进HSV-1在人类神经元中的潜伏期中可能起作用。
HSV-1 is a neurotropic pathogen associated with severe encephalitis, excruciating orofacial sensation, and other chronic neuropathic complications. After the acute infection, the virus may establish a lifelong latency in the neurons of trigeminal ganglia (TG) and other sensory and autonomic ganglia, including the dorsal root ganglia (DRG), etc. The reactivation occurred periodically by a variety of physical or emotional stressors. We have been developing a human DRG neuronal cell-culture model HD10.6, which mimics the mature neurons for latency and reactivation with robust neuronal physiology. We found that miR124 overexpression without acyclovir (ACV) could maintain the virus in a quiescent infection, with the accumulation of latency-associate transcript (LAT). The immediate-early (IE) gene ICP0, on the other hand, was very low and the latent viruses could be reactivated by trichostatin A (TSA) treatment. Together, these observations suggested a putative role of microRNA in promoting HSV-1 latency in human neurons.
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