title: Whole-Genome Sequence Analysis Reveals the Enterovirus D68 Isolates during the United States 2014 Outbreak Mainly Belong to a Novel Clade.
abstract: 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(pro) cleavage site between VP1 and 2A, whereas A4020G causes S1108G in a 3C(pro) cleavage site between 2B and 2C. The two functional mutations may alter the proteases' cleavage efficiency, leading to increased rate of viral replication and transmission. These provide insights into the evolution of epidemic EV-D68 strains.
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, New York, United States of America.
authors.forename: Weihua
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, New York, United States of America.|Department of Pathology and Clinical Laboratories, Westchester Medical Center, Valhalla, New York, United States of America.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pathology and Clinical Laboratories, Westchester Medical Center, Valhalla, New York, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuge
authors.affiliation: Division of Pediatric Infectious Disease, New York Medical College, Valhalla, New York, United States of America.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Nolan
authors.affiliation: Philips Research North America, Briarcliff Manor, New York, United States of America.
authors.forename: Nevenka
authors.initials: N
authors.lastname: Dimitrova
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, New York, United States of America.|Department of Pathology and Clinical Laboratories, Westchester Medical Center, Valhalla, New York, United States of America.
authors.forename: John T
authors.initials: JT
authors.lastname: Fallon
mesh_terms: D001483:Base Sequence; D016000:Cluster Analysis; D016002:Discriminant Analysis; D004196:Disease Outbreaks; D030016:Enterovirus D, Human / Q000235:genetics* / Q000302:isolation & purification; D004769:Enterovirus Infections / Q000453:epidemiology / Q000821:virology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000821:virology; D025341:Principal Component Analysis; D012367:RNA, Viral / Q000032:analysis / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000821:virology*; D012189:Retrospective Studies; D012621:Seasons; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D014481:United States / Q000453:epidemiology
chemical_list: D012367:RNA, Viral