Journal of Neurovirology ( IF 3.2 ) Pub Date : 2024-03-13 , DOI: 10.1007/s13365-024-01198-8 Joel A. Wood , Srilakshmi Chaparala , Cecilia Bantang , Ansuman Chattopadhyay , Maribeth A. Wesesky , Paul R. Kinchington , Vishwajit L. Nimgaonkar , David C. Bloom , Leonardo D’Aiuto
The neurogenic niches within the central nervous system serve as essential reservoirs for neural precursor cells (NPCs), playing a crucial role in neurogenesis. However, these NPCs are particularly vulnerable to infection by the herpes simplex virus 1 (HSV-1). In the present study, we investigated the changes in the transcriptome of NPCs in response to HSV-1 infection using bulk RNA-Seq, compared to those of uninfected samples, at different time points post infection and in the presence or absence of antivirals. The results showed that NPCs upon HSV-1 infection undergo a significant dysregulation of genes playing a crucial role in aspects of neurogenesis, including genes affecting NPC proliferation, migration, and differentiation. Our analysis revealed that the CREB signaling, which plays a crucial role in the regulation of neurogenesis and memory consolidation, was the most consistantly downregulated pathway, even in the presence of antivirals. Additionally, cholesterol biosynthesis was significantly downregulated in HSV-1-infected NPCs. The findings from this study, for the first time, offer insights into the intricate molecular mechanisms that underlie the neurogenesis impairment associated with HSV-1 infection.
中文翻译:
神经前体细胞转录组响应单纯疱疹病毒 1 感染的 RNA-Seq 时程分析
中枢神经系统内的神经生境是神经前体细胞(NPC)的重要储存库,在神经发生中发挥着至关重要的作用。然而,这些 NPC 特别容易受到单纯疱疹病毒 1 (HSV-1) 的感染。在本研究中,我们使用批量 RNA 测序研究了在感染后不同时间点以及存在或不存在抗病毒药物的情况下,与未感染样本相比,NPC 转录组响应 HSV-1 感染的变化。结果表明,HSV-1感染后的NPC会出现在神经发生方面发挥关键作用的基因的显着失调,包括影响NPC增殖、迁移和分化的基因。我们的分析表明,即使在存在抗病毒药物的情况下,CREB 信号传导在神经发生和记忆巩固的调节中发挥着至关重要的作用,也是最一致下调的途径。此外,HSV-1 感染的 NPC 中胆固醇生物合成显着下调。这项研究的结果首次深入了解了与 HSV-1 感染相关的神经发生损伤背后的复杂分子机制。