EV-D68 neurological disease: tipping the scales toward immunopathogenesis

Area of Science:

• Neurology
• Virology
• Immunology

Background:

• Enterovirus D68 (EV-D68) outbreaks have been associated with acute flaccid myelitis (AFM) in recent years.
• The precise mechanism driving EV-D68-induced AFM, specifically the damage to spinal cord motor neurons, remains unclear, with debate centering on direct viral damage versus immune-mediated injury.

Purpose of the Study:

• To investigate the role of immune cell infiltration versus direct viral infection in the pathogenesis of EV-D68-induced paralysis.
• To elucidate the immunopathogenic mechanisms underlying EV-D68-associated acute flaccid myelitis.

Main Methods:

• Utilized a neonatal wild-type (WT) mouse model to study EV-D68 infection.
• Employed cytokine-knockout and immune cell-depleted mouse models to assess the contribution of specific immune components to disease.

Main Results:

• Paralytic disease in the mouse model was attributed to the infiltration of immune cells into the spinal cord.
• Experiments involving cytokine-knockout or immune cell-depleted animals demonstrated a significant reduction in disease severity, supporting an immune-driven pathology.

Conclusions:

• The findings strongly suggest that immunopathogenesis, specifically immune cell infiltration into the spinal cord, plays a critical role in the development of EV-D68-induced acute flaccid myelitis.
• This research provides crucial insights into the mechanisms of EV-D68 pathogenesis, potentially guiding future therapeutic strategies for AFM.