{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:58:31Z","timestamp":1791388711859,"version":"4.3.3"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the late summer and the fall of 2014, the United States experienced an unprecedented outbreak of enterovirus D68 (EV-D68) infections. During the outbreak, we collected nasopharyngeal swab specimens from patients in the Lower Hudson Valley of New York. Here, we conduct a retrospective study on the genomic diversity of EV-D68 strains. We first employ a metagenomic shotgun sequencing protocol on a total of 93 clinical samples, including 21 negative controls, the results of which allow assembly of 20 EV-D68 genomes, six complete and 14 near-complete. We then investigate their genetic relationships, along with additional 20 EV-D68 strains having whole-genome sequences publicly available. Our comparative genomic analysis uncovers that the majority (26\/29) of EV-D68 strains circulating in the 2014 outbreak differ significantly from prior ones, have a main feature of three variables, C1817T, C3277A and A4020G and belong to a new clade. C3277A causes amino acid substitution T860N in the protease 2A<jats:sup><jats:italic>pro<\/jats:italic><\/jats:sup> cleavage site between VP1 and 2A, whereas A4020G causes S1108G in a 3C<jats:sup><jats:italic>pro<\/jats:italic><\/jats:sup> cleavage site between 2B and 2C. The two functional mutations may alter the proteases\u2019 cleavage efficiency, leading to increased rate of viral replication and transmission. These provide insights into the evolution of epidemic EV-D68 strains.<\/jats:p>","DOI":"10.1038\/srep15223","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T12:58:19Z","timestamp":1444913899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Whole-Genome Sequence Analysis Reveals the Enterovirus D68 Isolates during the United States 2014 Outbreak Mainly Belong to a Novel Clade"],"prefix":"10.1038","volume":"5","author":[{"given":"Weihua","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhuge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevenka","family":"Dimitrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Fallon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"BFsrep15223_CR1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1093\/oxfordjournals.aje.a120693","volume":"85","author":"JH Schieble","year":"1967","unstructured":"Schieble, J. 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Evaluation of a Real-Time Reverse Transcription-PCR Assay for Detection of Enterovirus D68 in Clinical Samples from an Outbreak in New York State in 2014. J Clin Microbiol 53, 1915\u20131920, 10.1128\/JCM.00358-15 (2015).","journal-title":"J Clin Microbiol"},{"key":"BFsrep15223_CR12","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1101\/gr.074492.107","volume":"18","author":"DR Zerbino","year":"2008","unstructured":"Zerbino, D. R. & Birney, E. Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res 18, 821\u2013829, 10.1101\/gr.074492.107 (2008).","journal-title":"Genome Res"},{"key":"BFsrep15223_CR13","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. 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