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November 19, 2025Frontiers in Microbiology5 citationsOpen Access

Strain-specific tropism and transcriptional responses of enterovirus D68 infection in human spinal cord organoids

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Population

Human spinal cord organoids derived from induced pluripotent stem cells, 24-day-old, n=12 pooled organoids…

Comparison

Infection with Enterovirus D68 strains… vs Mock-infected human spinal cord organoids.

Design

Preclinical

Follow-up

48 hours

Key result

EV-D68 strain US/IL/14-18952 preferentially infected neurons, while strain US/MA/18-23089 exhibited higher rates of infection in cycling astrocytes and oligodendrocyte progenitor cells.

Authors

NDNathânia DábillaSMSarah MayaCMColton McNinch

Discussion

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Overview

Supports hypothesis-generating research on EV-D68 tropism; leaves open clinical relevance for acute flaccid myelitis.

Structured PICO

P
Population
In vitro study utilizing human spinal cord organoids derived from induced pluripotent stem cells to investigate the cellular tropism and transcriptional responses of two Enterovirus D68 strains.
I
Intervention
Infection with Enterovirus D68 (EV-D68) strains US/IL/14-18952 (B2) or US/MA/18-23089 (B3) at 10^5 PFU for 48 hours.
C
Comparator
Mock-infected human spinal cord organoids.
O
Outcome
Cellular tropism and host transcriptional responses assessed by single-cell RNA sequencing (scRNA-seq).

Different strains of EV-D68 exhibit distinct cellular tropism and transcriptional responses in human spinal cord organoids, highlighting potential strain-specific mechanisms of acute flaccid myelitis pathogenesis.

Limitations

  • hSCO cells are relatively immature and represent a developing human spinal cord, which may differ from infection dynamics in a child.
  • Relatively low number of infected cells identified (~1.3-1.6% of total population), constraining the resolution of cell type-specific comparisons.
  • Analysis focused on a single early time point (48 hours post-infection), potentially missing delayed responses.
  • Lack of in vivo validation for the observed transcriptional shifts.
  • Single time point (48 hpi)

Cite This Study

Dábilla et al. (2025) studied Enterovirus D68 infection. Enterovirus D68 infection (strains US/IL/14-18952 and US/MA/18-23089) vs. Mock infection was evaluated on Cellular tropism and transcriptional responses. EV-D68 strain US/IL/14-18952 preferentially infected neurons, while strain US/MA/18-23089 exhibited higher rates of infection in cycling astrocytes and oligodendrocyte progenitor cells.

synapsesocial.com/papers/6a22565f806d0777c882a9c4https://doi.org/10.3389/fmicb.2025.1698639
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Contemporary enterovirus-D68 isolates infect human spinal cord organoids2023 · 31 citations
  2. 2Non-Polio Enterovirus A71 and D68 Infection of Human Neuromuscular Organoids Reveals Distinct Mechanisms of Neuromuscular Impairment2026
  3. 3Neurotropism of enterovirus D68 isolates is independent of sialic acid and is not a recently acquired phenotype2017 · 7 citations
  4. 4Spinal Cord Injury in Enterovirus D68 Infection: Mechanisms and Pathophysiology in a Mouse Model2025 · 1 citations
  5. 5Contemporary circulating enterovirus D68 strains show differential viral entry and replication in human neuronal cells2018