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Strain-Specific Tropism and Transcriptional Responses of Enterovirus D68 Infection in Human Spinal Cord Organoids

Nathânia Dábilla1, Sarah Maya2, Colton McNinch3

  • 1Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.

Biorxiv : the Preprint Server for Biology
|July 16, 2025
PubMed

Insights

Enterovirus D-68 (EV-D68) infects different spinal cord cells depending on the strain, impacting neurons or astrocytes and oligodendrocyte progenitor cells. This research clarifies EV-D68 tropism, aiding understanding of acute flaccid myelitis (AFM) pathogenesis.

Area of Science:

  • Neuroscience
  • Virology
  • Genomics

Background:

  • Acute flaccid myelitis (AFM) is a severe neurological condition linked to Enterovirus D-68 (EV-D68) infection.
  • The precise mechanisms and cellular targets of EV-D68 in the spinal cord remain unclear.

Purpose of the Study:

  • To investigate the cellular tropism and infection dynamics of EV-D68 in human spinal cord organoids (hSCOs).
  • To elucidate the host transcriptional responses to EV-D68 infection at single-cell resolution.

Main Methods:

  • Generation of human spinal cord organoids (hSCOs) from induced pluripotent stem cells (iPSCs).
  • Single-cell RNA sequencing (scRNA-seq) profiling of naive and EV-D68-infected hSCOs.
  • Infection of hSCOs with two distinct EV-D68 strains (B2 and B3).

Main Results:

  • hSCOs contain diverse neural and glial cell types, including neurons, astrocytes, oligodendrocyte progenitor cells (OPCs), and multipotent glial progenitor cells (mGPCs).
  • EV-D68 strain US/IL/14-18952 (B2) preferentially infected neurons.
  • EV-D68 strain US/MA/18-23089 (B3) showed higher tropism for cycling astrocytes and OPCs.

Conclusions:

  • Distinct EV-D68 strains exhibit specific cellular tropism within the human spinal cord.
  • These findings offer critical insights into the pathogenesis of EV-D68-associated AFM.
  • Understanding single-cell infection dynamics can guide the development of targeted therapeutic strategies.

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