A virus damages cell gateways and harms motor neurons
A common respiratory virus can devastate motor neurons in some children. New research reveals how: it damages the gateways of the cell nucleus. That same mechanism is relevant to aging nerve cells.
Enterovirus D68 (EV-D68) normally causes respiratory illness. But in a subset of infected children it leads to acute flaccid myelitis (AFM), a serious condition where motor neurons fail and muscles become paralyzed. Researchers wanted to understand why this virus targets motor neurons so selectively.
They focused on the nuclear pore complex (NPC): a structure in the membrane surrounding the cell nucleus that controls what enters and exits the cell. The NPC acts as a kind of customs checkpoint for the cell. The study, published in eLife, shows that a specific protein from EV-D68, the 2A protease, damages this pore complex by directly cleaving two of its components: Nup98 and POM121.
Connection to aging nerve cells
This matters beyond AFM treatment. Disruptions in the nuclear pore complex have also been linked to neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). During aging, NPC structures increasingly malfunction or degrade. The mechanism EV-D68 exploits resembles processes that also play a role in ordinary nerve cell aging.
The researchers also tested a potential protective intervention. An inhibitor called telaprevir reduced the toxicity of the 2A protease toward motor neurons without fully blocking viral replication. This suggests the protease causes damage independently of the virus itself.
What this opens for therapy
The finding that the 2A protease is independently toxic to motor neurons offers a potential therapeutic entry point, for AFM as well as for broader forms of motor neuron degeneration. Whether telaprevir or similar compounds can be used clinically requires further investigation. The study is based on cell models and stem cell-derived neurons, not clinical patient data.