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August 3, 2023mBioOpen Access

Contemporary enterovirus-D68 isolates infect human spinal cord organoids

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Why the study?

The mechanisms by which EV-D68 targets the central nervous system are unknown, and a human model is needed because enteroviruses do not routinely infect other animal species.

Population

Two human spinal cord organoid-based models derived from iPSC lines

Comparison

Contemporary strains vs a historic strain of EV-D68 and echovirus 11

Design

In vitro laboratory study

Follow-up

At least 2 weeks

Key result

Human spinal cord organoids can be productively infected with contemporary EV-D68 strains without appreciable cytopathic effect, unlike echovirus 11 which causes significant structural destruction.

Authors

GAGabrielle AgugliaCCCarolyn B. CoyneTDTerence S. Dermody

Discussion

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Overview

EV-D68 infects hSCOs without cytopathy, implicating immune-mediated AFM pathogenesis; leaves open translation to human disease.

Structured PICO

P
Population
Two human spinal cord organoid (hSCO)-based models derived from induced pluripotent stem cell (iPSC) lines (one primarily spinal motor neurons, another comprising multiple neuronal cell lineages including motor neurons, interneurons, and glial cells)
E
Exposure
Infection with contemporary strains of Enterovirus D68 (EV-D68)
C
Comparator
Infection with a historic strain of EV-D68 or echovirus 11
O
Outcome
Productive infection, extracellular virus production, and cytopathic effect/apoptosis

Contemporary EV-D68 strains productively infect human spinal cord organoids without causing direct cytopathic effect, suggesting secondary immune responses may drive neuronal cell death in acute flaccid myelitis.

Cite This Study

Aguglia et al. (2023) studied Enterovirus D68 infection / Acute flaccid myelitis. Enterovirus D68 (contemporary strains) vs. Historic strain of EV-D68 / Echovirus 11 was evaluated on Productive infection and cytopathic effect. Human spinal cord organoids can be productively infected with contemporary EV-D68 strains without appreciable cytopathic effect, unlike echovirus 11 which causes significant structural destruction.

synapsesocial.com/papers/6a92e9cde62ac992d65c18b2https://doi.org/10.1128/mbio.01058-23
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