Related Experiment Video

Updated: Jun 19, 2026

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
08:53

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Published on: May 16, 2017

Enterovirus D68 2A protease causes nuclear pore complex dysfunction and independently contributes to motor neuron

Katrina M Zinn1, Mathew W McLaren1, Michael T Imai1

  • 1Hugo W. Moser Research Institute, Michael V. Johnston Center for Developmental Neuroscience, Kennedy Krieger Institute, Baltimore, United States.

Elife
|June 18, 2026
PubMed

Insights

Enterovirus D68 proteases disrupt the nuclear pore complex, leading to motor neuron toxicity. Targeting these proteases may offer a new therapeutic strategy for acute flaccid myelitis.

Area of Science:

  • Neurovirology
  • Molecular Biology
  • Cell Biology

Background:

  • Enterovirus D68 (EV-D68) causes acute flaccid myelitis (AFM) by targeting spinal motor neurons.
  • Mechanisms of EV-D68 neurotoxicity and selective motor neuron death remain unclear.
  • Nuclear pore complex (NPC) dysfunction is linked to neurodegeneration and altered during picornavirus infections.

Purpose of the Study:

  • To investigate the impact of EV-D68 proteases on NPC composition and function.
  • To determine if EV-D68 proteases contribute to motor neuron toxicity.

Main Methods:

  • Analysis of NPC composition following EV-D68 protease expression.
  • Reporter assays to assess nuclear transport and NPC permeability.
  • Toxicity assays using induced pluripotent stem cell-derived motor neurons and a protease inhibitor.

Main Results:

  • EV-D68 2A and 3C proteases cleave key nucleoporins, including Nup98 and POM121.
  • The 2A protease (2Apro) inhibits protein import and disrupts NPC permeability but not RNA export.
  • 2Apro exhibits direct toxicity to motor neurons, which is rescued by a specific inhibitor.

Conclusions:

  • EV-D68 proteases significantly alter NPC integrity and function.
  • 2Apro-mediated NPC disruption contributes to motor neuron death in AFM.
  • NPC components or 2Apro are potential therapeutic targets for AFM.
Keywords:
acute flaccid myelitisenterovirushumaninfectious diseasemicrobiologyneurosciencenuclear pore complexvirus-host interactionviruses

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