RNA-Seq time-course analysis of neural precursor cell transcriptome in response to herpes simplex Virus-1 infection

IF 2.3 4区 医学 Q3 NEUROSCIENCES Journal of NeuroVirology 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
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Abstract

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.

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针对单纯疱疹病毒-1 感染的神经前体细胞转录组的 RNA-Seq 时程分析
中枢神经系统内的神经源龛是神经前体细胞(NPCs)的重要储库,在神经发生过程中起着至关重要的作用。然而,这些神经前体细胞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-Seq 研究了 NPCs 在感染后不同时间点、有无抗病毒药物的情况下,与未感染样本相比,在 HSV-1 感染下转录组发生的变化。结果表明,HSV-1 感染后,NPC 在神经发生过程中起关键作用的基因,包括影响 NPC 增殖、迁移和分化的基因,都发生了明显的失调。我们的分析表明,即使在使用抗病毒药物的情况下,在神经发生和记忆巩固的调控中发挥关键作用的 CREB 信号转导也是最持续下调的途径。此外,HSV-1 感染的鼻咽癌中胆固醇的生物合成也显著下调。这项研究的结果首次揭示了HSV-1感染导致神经发生障碍的复杂分子机制。
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来源期刊
Journal of NeuroVirology
Journal of NeuroVirology 医学-病毒学
CiteScore
6.60
自引率
3.10%
发文量
77
审稿时长
6-12 weeks
期刊介绍: The Journal of NeuroVirology (JNV) provides a unique platform for the publication of high-quality basic science and clinical studies on the molecular biology and pathogenesis of viral infections of the nervous system, and for reporting on the development of novel therapeutic strategies using neurotropic viral vectors. The Journal also emphasizes publication of non-viral infections that affect the central nervous system. The Journal publishes original research articles, reviews, case reports, coverage of various scientific meetings, along with supplements and special issues on selected subjects. The Journal is currently accepting submissions of original work from the following basic and clinical research areas: Aging & Neurodegeneration, Apoptosis, CNS Signal Transduction, Emerging CNS Infections, Molecular Virology, Neural-Immune Interaction, Novel Diagnostics, Novel Therapeutics, Stem Cell Biology, Transmissable Encephalopathies/Prion, Vaccine Development, Viral Genomics, Viral Neurooncology, Viral Neurochemistry, Viral Neuroimmunology, Viral Neuropharmacology.
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