Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons has contributed to this knowledge gap. In this study, we utilize advances in stem cell technology to characterize rabies infection in human stem cell-derived neurons. We show key cellular features of rabies infection in our human neural cultures, including upregulation of inflammatory chemokines, lack of neuronal apoptosis, and axonal transmission of viruses in neuronal networks. In addition, we highlight specific differences in cellular pathogenesis between laboratory-adapted and field strain lyssavirus. This study therefore defines the first stem cell-derived ex-vivo model system to study rabies pathogenesis in human neurons. This new model system demonstrates the potential for enabling an increased understanding of molecular mechanisms in human rabies, which could lead to improved control methods.

中文翻译：

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在人类干细胞衍生的神经培养物中模拟狂犬病病毒感染。


狂犬病是一种由狂犬病病毒引起的人畜共患神经系统感染，持续造成毁灭性的人类生命损失。人类神经元狂犬病发病机制的许多方面尚不清楚。缺乏适当的离体模型来研究人类神经元中的狂犬病感染，导致了这一知识差距。在这项研究中，我们利用干细胞技术的进步来表征人类干细胞衍生神经元中的狂犬病感染。我们在人类神经培养物中展示了狂犬病感染的关键细胞特征，包括炎症趋化因子的上调、神经元细胞凋亡的缺乏以及神经元网络中病毒的轴突传播。此外，我们还强调了实验室适应型狂犬病病毒株和野外狂犬病病毒株在细胞发病机制上的具体差异。因此，这项研究定义了第一个干细胞衍生的离体模型系统，用于研究人类神经元中的狂犬病发病机制。这个新模型系统展示了增强对人类狂犬病分子机制的了解的潜力，这可能会导致控制方法的改进。