{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:59:23Z","timestamp":1792159163673,"version":"4.4.0"},"reference-count":108,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS101208"],"award-info":[{"award-number":["NS101208"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI136403"],"award-info":[{"award-number":["AI136403"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v11090821","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T03:22:36Z","timestamp":1567653756000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8373-4311","authenticated-orcid":false,"given":"Alison M.","family":"Hixon","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6517-4966","authenticated-orcid":false,"given":"Joshua","family":"Frost","sequence":"additional","affiliation":[{"name":"Department of Immunology &amp; Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3936-6849","authenticated-orcid":false,"given":"Michael J.","family":"Rudy","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5830-3491","authenticated-orcid":false,"given":"Kevin","family":"Messacar","sequence":"additional","affiliation":[{"name":"Hospital Medicine and Pediatric Infectious Disease Sections, Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA"},{"name":"Children\u2019s Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Tyler","sequence":"additional","affiliation":[{"name":"Department of Immunology &amp; Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA"},{"name":"Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA"},{"name":"Division of Infectious Disease, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA"},{"name":"Neurology Service, Rocky Mountain VA Medical Center, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virol.2005.09.015","article-title":"One hundred years of poliovirus pathogenesis","volume":"344","author":"Racaniello","year":"2006","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/QCO.0000000000000187","article-title":"The epidemiology of non-polio enteroviruses: Recent advances and outstanding questions","volume":"28","author":"Parker","year":"2015","journal-title":"Curr. 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