Wednesday, October 29, 2014

EID Journal: Genome Sequence of Enterovirus D68 from St. Louis


# 9262



In late August we began to track an unusual late summer outbreak of Enterovirus D68, which was first reported in Illinois and Missouri, but which quickly spread across the nation (see Kansas City Outbreak Identified As HEV 68).   Although EV-D68 – one of the dozens of non-polio enteroviruses – had first been indentified 50 years ago, until the past few years it has only rarely been reported in North America.


In 2011 – in MMWR: Clusters Of HEV68 Respiratory Infections 2008-2010 – we looked at a half dozen  HV 68 associated clusters which occurred in Asia, Europe, and the United States during 2008--2010.


A few excerpts from that report:


HEV68 infection was associated with respiratory illness ranging from relatively mild illness that did not require hospitalization to severe illness requiring intensive care and mechanical ventilation. Three cases, two in the Philippines and one in Japan, were fatal. In these six clusters, HEV68 disproportionately occurred among children.

Previous outbreaks have all appeared to be limited to a few dozen people, although testing for the virus has always been extremely limited.  How pervasive this virus really is in the population is largely unknown. 


That said, the rapid nationwide spread of EV-D68 over the past three months is unusual, and a coincident rise in neurological illness and limb weakness (see CDC HAN: Acute Neurologic Illness with Focal Limb Weakness of Unknown Etiology in Children) has raised questions as to whether this virus has recently changed.  


A causal link between these paralysis cases and EV-D68 has not yet been established.


Yesterday, researchers from Washington University School of Medicine in St. Louis published a letter in the CDC’s EID journal, describing their genetic sequencing of the EV-D68 virus collected from patients in St. Louis.

There is not a lot of older sequence data to compare the current strain with – making it difficult to pinpoint any changes that may have contributed to its severity or rapid spread.  Having this new data will help track future changes and identify different strains currently in circulation.  According to a news release from the University:


“The CDC has published some additional genomes from Missouri, Illinois and Kentucky,” said first author Kristine M. Wylie, PhD, research instructor in pediatrics. “The Missouri genomes, including ours, are all very similar, but the Illinois and Kentucky genomes are different from the Missouri types, suggesting there are some distinct strains circulating in the U.S. right now.”

Wylie also pointed out the importance of continuing to characterize the genetic features of this virus and monitor the health of patients with the D68 strain.

“Until recently, this virus has been pretty rare,” she said. “It would be helpful to have more data about the virus and the patients so that we can start to associate the genetic features of the virus with the severity of the disease.”


Some excerpts from the EID Letter follow:


Volume 21, Number 1—January 2015

Genome Sequence of Enterovirus D68 from St. Louis, Missouri, USA

To the Editor: During the current (2014) enterovirus/rhinovirus season in the United States, enterovirus D68 (EV-D68) is circulating at an unprecedented level. As of October 6, 2014, the Centers for Disease Control and Prevention (CDC) had confirmed 594 cases of EV-D68 infection in 43 states and the District of Columbia (; the actual number of cases was undoubtedly much higher. In mid-August, hospitals in Missouri and Illinois noticed an increased number of patients with severe respiratory illness (1). We observed this pattern at St. Louis Children’s Hospital in St. Louis, Missouri.

Resources for studying this virus are limited. Before the current season, only 7 whole-genome sequences and 5 additional complete coding sequences of the virus were available. Therefore, determining whether there are genomic elements associated with rapid spread or severe and unusual disease was not possible.

To address these limitations, we determined the complete coding sequence of 1 strain from St. Louis by using high-throughput sequencing of nucleic acid from a clinical sample. To evaluate the sequence diversity in EV-D68 strains circulating in the St. Louis metropolitan area, we also generated partial-genome sequences from 8 more EV-D68–positive clinical samples from St. Louis. During the preparation of this article, CDC generated and submitted to GenBank 7 complete or nearly complete genome sequences from viruses obtained from the Midwest. We documented the diversity of the sequences of strains from St. Louis and compared them to publicly available sequences.


Comparison of the virus protein 1 sequence with that of publicly available sequences indicated that the strain from St. Louis and the strain from Missouri (CDC) cluster with virus strains identified in Europe and Asia within the past several years (Figure, panel B). The St. Louis virus shared 97%–99% aa sequence identity with all other sequenced strains. We observed little variation in the strains from St. Louis because they shared 98%–99% nt sequence identity (Technical Appendix[PDF - 78 KB - 4 pages] Figure).

We provide a genome sequence from the 2014 outbreak of EV-D68 infection in St. Louis, Missouri. This sequence seems to be highly representative of the strains circulating in St. Louis during this time because the other genomes we partially sequenced are very similar. To our knowledge, no amino acids have been associated with virulence or increased infectivity of EV-D68; therefore, we cannot associate the changes we observed in these genomes to phenotypic traits. Because changes in the 5′ untranslated region have the potential to affect the rate of replication (810), it is possible that minor genome changes are responsible for the rapid spread and high severity of disease in 2014. Correlation between clinical features of patients in conjunction with additional genomic analysis might provide further insight into the pathogenetic determinants of this strain. Therefore the genome sequence of EV-D68 determined from the 2014 outbreak in St. Louis, Missouri, provides a resource for tracking and genomic comparison of this rapidly spreading virus.

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