Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA.
Graduate School in Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA.
Cells. 2021 Nov 18;10(11):3218. doi: 10.3390/cells10113218.
Astrocytes are a main target of JC polyomavirus (JCPyV) in the central nervous system (CNS), where the destruction of these cells, along with oligodendrocytes, leads to the fatal disease progressive multifocal leukoencephalopathy (PML). There is no cure currently available for PML, so it is essential to discover antivirals for this aggressive disease. Additionally, the lack of a tractable in vivo models for studying JCPyV infection makes primary cells an accurate alternative for elucidating mechanisms of viral infection in the CNS. This research to better understand the signaling pathways activated in response to JCPyV infection reveals and establishes the importance of the PI3K/AKT/mTOR signaling pathway in JCPyV infection in primary human astrocytes compared to transformed cell lines. Using RNA sequencing and chemical inhibitors to target PI3K, AKT, and mTOR, we have demonstrated the importance of this signaling pathway in JCPyV infection of primary astrocytes not observed in transformed cells. Collectively, these findings illuminate the potential for repurposing drugs that are involved with inhibition of the PI3K/AKT/mTOR signaling pathway and cancer treatment as potential therapeutics for PML, caused by this neuroinvasive virus.
星形胶质细胞是中枢神经系统（CNS）中 JC 多瘤病毒（JCPyV）的主要靶标，这些细胞与少突胶质细胞一起被破坏，导致致命的进行性多灶性白质脑病（PML）。目前尚无针对 PML 的治愈方法，因此发现针对这种侵袭性疾病的抗病毒药物至关重要。此外，由于缺乏用于研究 JCPyV 感染的可处理的体内模型，原代细胞成为阐明 CNS 中病毒感染机制的准确替代方法。这项旨在更好地了解针对 JCPyV 感染而激活的信号通路的研究表明并确立了在原代人星形胶质细胞中，与转化细胞系相比，PI3K/AKT/mTOR 信号通路在 JCPyV 感染中的重要性。通过使用 RNA 测序和针对 PI3K、AKT 和 mTOR 的化学抑制剂，我们已经证明了在原代星形胶质细胞中，该信号通路在 JCPyV 感染中的重要性，而在转化细胞中则没有观察到这种作用。总的来说，这些发现阐明了将涉及抑制 PI3K/AKT/mTOR 信号通路和癌症治疗的药物重新用于治疗由这种神经侵袭性病毒引起的 PML 的潜力。
Zotero 插件