Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection.

Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection.
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DOI:
10.1080/15476278.2022.2055354
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发表时间:
2022-12-31
期刊:
影响因子:
2.3
通讯作者:
D'Aiuto L
D'Aiuto L
中科院分区:
工程技术4区
文献类型:
--
作者:
Zheng W;Benner EM;Bloom DC;Muralidaran V;Caldwell JK;Prabhudesai A;Piazza PA;Wood J;Kinchington PR;Nimgaonkar VL;D'Aiuto L

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脑炎是由单纯疱疹病毒 1 (HSV-1) 引起的最重要的中枢神经系统 (CNS) 疾病,可能会给接受阿昔洛韦治疗的幸存者带来长期后遗症,其原因尚不清楚。 HSV-1 对中枢神经系统中富含神经前体细胞 (NPC) 的神经源性生态位表现出趋向性,而神经前体细胞在神经发生中发挥着关键作用。 NPC 对 HSV-1 敏感。关于 HSV-1 对人类神经发生的影响的信息很少。我们调查了两个个体的 NPC 的 HSV-1 感染情况。我们的结果表明:(i)HSV-1 在不同程度上损害了这两个受试者的 NPC 的增殖、自我更新,甚至在更大程度上损害了迁移; (ii)金标准抗疱疹药物阿昔洛韦(ACV)的保护作用随病毒剂量的不同而变化,并且是不完全的。这两个个体派生的 NPC 的功效也存在差异。这些结果表明,HSV-1 对 NPC 神经发生方面的影响可能因个体而异,即使在阿昔洛韦存在的情况下也是如此,这可能导致脑炎幸存者认知后遗症的异质性。有必要对大量个体的鼻咽癌细胞系进行进一步分析。
Encephalitis, the most significant of the central nervous system (CNS) diseases caused by Herpes simplex virus 1 (HSV-1), may have long-term sequelae in survivors treated with acyclovir, the cause of which is unclear. HSV-1 exhibits a tropism toward neurogenic niches in CNS enriched with neural precursor cells (NPCs), which play a pivotal role in neurogenesis. NPCs are susceptible to HSV-1. There is a paucity of information regarding the influence of HSV-1 on neurogenesis in humans. We investigated HSV-1 infection of NPCs from two individuals. Our results show (i) HSV-1 impairs, to different extents, the proliferation, self-renewing, and, to an even greater extent, migration of NPCs from these two subjects; (ii) The protective effect of the gold-standard antiherpetic drug acyclovir (ACV) varies with viral dose and is incomplete. It is also subject to differences in terms of efficacy of the NPCs derived from these two individuals. These results suggest that the effects of HSV-1 may have on aspects of NPC neurogenesis may vary among individuals, even in the presence of acyclovir, and this may contribute to the heterogeneity of cognitive sequelae across encephalitis survivors. Further analysis of NPC cell lines from a larger number of individuals is warranted.
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