Publications
Citation
Tan Y, Hassan F, Schuster JE, Simenauer A, Selvarangan R, Halpin RA, Lin X, Fedorova N, Stockwell TB, Tsan-Yuk Lam T, Chappell JD, Hartert TV, Holmes EC, Das SR
Molecular Evolution and Intra-clade Recombination of Enterovirus D68 During the 2014 Outbreak in the United States.
Journal of Virology. 2015 Dec 09;
Abstract
In August 2014 an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, Missouri collected during the 2014 outbreak. With these data in-hand we performed phylogenetic analyses of complete genome and VP1 capsid protein sequences. Notably, we observed considerable genetic diversity among EV-D68 isolates in Kansas City, manifest as phylogenetically distinct lineages, indicative of multiple introductions of this virus into the city. In addition, we identified an inter-subclade recombination event within EV-D68, the first recombinant in this virus reported to date. Finally, we found no significant association between EV-D68 genetic variation, either lineages or individual mutations, and a variety of demographic and clinical variables, suggesting that host factors likely play a major role in determining disease severity. Overall, our study revealed the complex pattern of viral evolution within a single geographic locality during a single outbreak, which has implications for the design of effective intervention and prevention strategies.