Key result
The majority (26 of 29) of EV-D68 strains circulating in the 2014 US outbreak belonged to a novel clade characterized by three mutations (C1817T, C3277A, and A4020G) that may alter viral replication and transmission.
Observational (n=93)
No
p-value: p=0.00016
Whole-genome sequencing of EV-D68 isolates from the 2014 US outbreak reveals a novel clade with specific protease cleavage site mutations that may alter viral replication and transmission.
Identifies novel EV-D68 clade in 2014 outbreak; leaves open functional impact of mutations and need for prospective validation.
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.
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Huang et al. (2015) conducted an observational in Enterovirus D68 infection (n=93). 2014 US outbreak EV-D68 strains vs. EV-D68 strains from before 2014 or outside the US was evaluated on Clustering into a novel clade characterized by C1817T, C3277A, and A4020G mutations (p=0.00016). The majority (26 of 29) of EV-D68 strains circulating in the 2014 US outbreak belonged to a novel clade characterized by three mutations (C1817T, C3277A, and A4020G) that may alter viral replication and transmission.
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