EV-D68 neurological disease: tipping the scales toward immunopathogenesis
Peter W. Krug
Peter W. Krug
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Commentary

EV-D68 neurological disease: tipping the scales toward immunopathogenesis

Abstract

Over the last decade, there have been multiple outbreaks of enterovirus D68 (EV-D68) disease and associated cases of acute flaccid myelitis (AFM). The underlying cause of EV-D68–induced AFM is contentious; whether spinal cord motor neurons are damaged by direct viral infection, infiltration of immune cells, or a combination of both is not clear. In this issue of the JCI, Woods Acevedo and coworkers used a neonatal WT mouse model of EV-D68 infection to attribute paralytic disease to immune cell infiltration into the spinal cord. The results of their work in cytokine-knockout or immune cell–depleted animals effectively argue that immunopathogenesis plays an integral role in EV-D68–induced AFM.

Authors

Peter W. Krug

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Figure 1

Neonatal WT mouse intracranial infection and CNS disease can parallel EV-D68 infection and progression to AFM.

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Neonatal WT mouse intracranial infection and CNS disease can parallel EV...
Mice infected with neurovirulent EV-D68 via intracranial (IC) injection undergo viral replication in the brain. In natural infection in children, EV-D68 enters via the intranasal (IN) route and replicates in the upper respiratory tract (URT). In most neonatal mice and infrequently in children, the virus spreads to the spinal cord, causing inflammation and eliciting chemokines that attract and activate T cells and macrophages. Activated T cells and macrophages infiltrate the areas of virus-induced inflammation at the spinal cord, damaging motor neurons and causing limb paralysis. Woods Acevedo et al. (7) reveal that Ccr2–/– neonatal mice and CD8+ T cell–depleted neonatal mice are unable to respond to the inflammation and chemokines elicited by EV-D68 dissemination to the spinal cord, preventing the onset of paralysis. In children, early EV-D68 diagnosis and intervention with specific antiviral and immunomodulatory countermeasures could prevent recruitment of immune cells to the CNS, thereby blocking the onset of AFM.