ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
Strain-Specific Tropism and Transcriptional Responses of Enterovirus D68 Infection in Human Spinal Cord Organoids
Provisionally accepted
- 1National Institute of Allergy and Infectious Diseases Division of Intramural Research, Bethesda, United States
- 2University of Pittsburgh School of Medicine, Pittsburgh, United States
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The mechanisms by which Enterovirus D68 (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 include diverse cell types, including neurons, astrocytes, oligodendrocyte progenitor cells (OPCs), and multipotent glial progenitor cells (mGPCs). Upon infection with two EV-D68 strains, US/IL/14-18952 (a B2 strain) and US/MA/18-23089 (a B3 strain), we observed distinct viral tropism and host transcriptional responses. Notably, US/IL/14-18952 showed a significant preference for neurons, while US/MA/18-23089 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.
Keywords: Enterovirus, EV-D68, Single-cell sequence (scRNA-seq), systems biology, Organoids, Spinal Cord
Received: 03 Sep 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Dabilla, Maya, McNinch, Eddens, Dolan and Freeman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Patrick T. Dolan, patrick.dolan@nih.gov
Megan Culler Freeman, megan.freeman@chp.edu
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