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Open AccessReview

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

1
Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045, USA
2
Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA
3
Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA
4
Hospital Medicine and Pediatric Infectious Disease Sections, Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA
5
Children’s Hospital Colorado, Aurora, CO 80045, USA
6
Division of Infectious Disease, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
7
Neurology Service, Rocky Mountain VA Medical Center, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Viruses 2019, 11(9), 821; https://doi.org/10.3390/v11090821
Received: 31 July 2019 / Revised: 28 August 2019 / Accepted: 29 August 2019 / Published: 4 September 2019
(This article belongs to the Special Issue Neuroinvasive Viral Infections)
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. View Full-Text
Keywords: enterovirus D68; acute flaccid myelitis; paralysis; neuropathogenesis; mouse models; experimental models enterovirus D68; acute flaccid myelitis; paralysis; neuropathogenesis; mouse models; experimental models
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MDPI and ACS Style

Hixon, A.M.; Frost, J.; Rudy, M.J.; Messacar, K.; Clarke, P.; Tyler, K.L. Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review. Viruses 2019, 11, 821. https://doi.org/10.3390/v11090821

AMA Style

Hixon AM, Frost J, Rudy MJ, Messacar K, Clarke P, Tyler KL. Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review. Viruses. 2019; 11(9):821. https://doi.org/10.3390/v11090821

Chicago/Turabian Style

Hixon, Alison M.; Frost, Joshua; Rudy, Michael J.; Messacar, Kevin; Clarke, Penny; Tyler, Kenneth L. 2019. "Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review" Viruses 11, no. 9: 821. https://doi.org/10.3390/v11090821

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