Dábilla Nathânia, Maya Sarah, McNinch Colton, Eddens Taylor, Dolan Patrick T, Freeman Megan Culler
Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.
University of Pittsburgh School of Medicine, Department of Pediatrics, Division of Infectious Diseases, Pittsburgh, PA, USA.
bioRxiv. 2025 Jun 27:2025.06.27.661907. doi: 10.1101/2025.06.27.661907.
The mechanisms by which D-68 (EV-D68) infection leads to acute flaccid myelitis (AFM), a severe neurological condition characterized by sudden muscle weakness and paralysis, remain poorly understood. To investigate the cellular tropism and infection dynamics of EV-D68, we profiled naive and EV-D68-infected human spinal cord organoids (hSCOs) derived from induced pluripotent stem cells (iPSCs) using single-cell RNA sequencing (scRNA-seq). Examining the cellular composition of healthy hSCOs, we found that hSCOs comprise diverse cell types, including neurons, astrocytes, oligodendrocyte progenitor cells (OPCs), and multipotent glial progenitor cells (mGPCs). Upon infection with two EV-D68 strains, (a B2 strain) and (a B3 strain), we observed distinct viral tropism and host transcriptional responses. Notably, showed a significant preference for neurons, while exhibited higher rates of infection in cycling astrocytes and OPCs. These findings provide novel insights into the host cell tropism of EV-D68 in the spinal cord, offering insight into the potential mechanisms underlying AFM pathogenesis. Understanding the dynamics of infection at single-cell resolution will inform future therapeutic strategies aimed at mitigating the neurological impact of enteroviral infections.
D-68（肠道病毒D68型，EV-D68）感染导致急性弛缓性脊髓炎（AFM）的机制仍知之甚少，AFM是一种以突发肌肉无力和瘫痪为特征的严重神经系统疾病。为了研究EV-D68的细胞嗜性和感染动态，我们使用单细胞RNA测序（scRNA-seq）对源自诱导多能干细胞（iPSC）的未感染和EV-D68感染的人脊髓类器官（hSCO）进行了分析。通过检查健康hSCO的细胞组成，我们发现hSCO包含多种细胞类型，包括神经元、星形胶质细胞、少突胶质前体细胞（OPC）和多能神经胶质前体细胞（mGPC）。在用两种EV-D68毒株（一种B2毒株和一种B3毒株）感染后，我们观察到了不同的病毒嗜性和宿主转录反应。值得注意的是，[B2毒株]对神经元表现出明显的偏好，而[B3毒株]在活跃的星形胶质细胞和OPC中表现出更高的感染率。这些发现为脊髓中EV-D68的宿主细胞嗜性提供了新的见解，有助于深入了解AFM发病机制的潜在机制。在单细胞分辨率下了解感染动态将为未来旨在减轻肠道病毒感染对神经系统影响的治疗策略提供信息。
