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Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review.
Viruses. 2019 09 04; 11(9)V

Abstract

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.

Authors+Show Affiliations

Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA.Hospital Medicine and Pediatric Infectious Disease Sections, Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA. Kevin.Messacar@childrenscolorado.org. Children's Hospital Colorado, Aurora, CO 80045, USA. Kevin.Messacar@childrenscolorado.org.Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA. penny.clarke@cuanschutz.edu.Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Division of Infectious Disease, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA. Neurology Service, Rocky Mountain VA Medical Center, Aurora, CO 80045, USA.

Pub Type(s)

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

Language

eng

PubMed ID

31487952

Citation

Hixon, Alison M., et al. "Understanding Enterovirus D68-Induced Neurologic Disease: a Basic Science Review." Viruses, vol. 11, no. 9, 2019.
Hixon AM, Frost J, Rudy MJ, et al. Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review. Viruses. 2019;11(9).
Hixon, A. M., Frost, J., Rudy, M. J., Messacar, K., Clarke, P., & Tyler, K. L. (2019). Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review. Viruses, 11(9). https://doi.org/10.3390/v11090821
Hixon AM, et al. Understanding Enterovirus D68-Induced Neurologic Disease: a Basic Science Review. Viruses. 2019 09 4;11(9) PubMed PMID: 31487952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review. AU - Hixon,Alison M, AU - Frost,Joshua, AU - Rudy,Michael J, AU - Messacar,Kevin, AU - Clarke,Penny, AU - Tyler,Kenneth L, Y1 - 2019/09/04/ PY - 2019/07/31/received PY - 2019/08/28/revised PY - 2019/08/29/accepted PY - 2019/9/7/entrez PY - 2019/9/7/pubmed PY - 2020/9/4/medline KW - acute flaccid myelitis KW - enterovirus D68 KW - experimental models KW - mouse models KW - neuropathogenesis KW - paralysis JF - Viruses JO - Viruses VL - 11 IS - 9 N2 - 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. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/31487952/Understanding_Enterovirus_D68_Induced_Neurologic_Disease:_A_Basic_Science_Review_ L2 - https://www.mdpi.com/resolver?pii=v11090821 DB - PRIME DP - Unbound Medicine ER -