Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review

Viruses. 2019 Sep 4;11(9):821. doi: 10.3390/v11090821.


In 2014, the United States (US) experienced an unprecedented epidemic of enterovirus D68 (EV-D68)-induced respiratory disease that was temporally associated with the emergence of acute flaccid myelitis (AFM), a paralytic disease occurring predominantly in children, that has a striking resemblance to poliomyelitis. Although a definitive causal link between EV-D68 infection and AFM has not been unequivocally established, rapidly accumulating clinical, immunological, and epidemiological evidence points to EV-D68 as the major causative agent of recent seasonal childhood AFM outbreaks in the US. This review summarizes evidence, gained from in vivo and in vitro models of EV-D68-induced disease, which demonstrates that contemporary EV-D68 strains isolated during and since the 2014 outbreak differ from historical EV-D68 in several factors influencing neurovirulence, including their genomic sequence, their receptor utilization, their ability to infect neurons, and their neuropathogenicity in mice. These findings provide biological plausibility that EV-D68 is a causal agent of AFM and provide important experimental models for studies of pathogenesis and treatment that are likely to be difficult or impossible in humans.

Keywords: acute flaccid myelitis; enterovirus D68; experimental models; mouse models; neuropathogenesis; paralysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Central Nervous System Viral Diseases / epidemiology
  • Central Nervous System Viral Diseases / virology
  • Disease Outbreaks
  • Enterovirus D, Human / genetics
  • Enterovirus D, Human / physiology*
  • Enterovirus Infections / epidemiology
  • Enterovirus Infections / virology*
  • Humans
  • Myelitis / epidemiology
  • Myelitis / virology
  • Nervous System Diseases / epidemiology
  • Nervous System Diseases / virology*
  • Neuromuscular Diseases / epidemiology
  • Neuromuscular Diseases / virology
  • United States / epidemiology

Supplementary concepts

  • acute flaccid myelitis