Worldwide emergence of multiple clades of enterovirus 68

Abstract

Human enterovirus 68 (EV-D68) is a historically rarely reported virus linked with respiratory disease. In the past 3 years, a large increase in respiratory disease associated with EV-D68 has been reported, with documented outbreaks in North America, Europe and Asia. In several outbreaks, genetic differences were identified among the circulating strains, indicating the presence of multiple clades. In this report, we analyse archived and novel EV-D68 strains from Africa and the USA, obtained from patients with respiratory illness. Phylogenetic analysis of all EV-D68 sequences indicates that, over the past two decades, multiple clades of the virus have emerged and spread rapidly worldwide. All clades appear to be currently circulating and contributing to respiratory disease.

Fig. 1.

Evolutionary history of EV-D68 based on complete VP1 sequences. The maximum clade credibility tree is shown with BPP values of 0.7–0.8 and 0.9–1.0 indicated by ⧫ and ◊ at the nodes, respectively. Clades A, B and C are indicated and supported by BPP = 1.0. The Bayesian skyline plots (BSPs) are shown for the overall dataset (bottom left) and for clades A, B and C. The black line indicates the median relative genetic diversity (log₁₀ scale) over time and the grey curves represent the upper and lower 95 % HPD intervals. • at the tips of the branches indicates novel sequences generated in this study. The vertical arrow indicates the branch along which the VP1 asparagine deletion occurred; † indicates the Fermon strain (1962), and * indicates the initial clade A strain from Maryland, USA (1999).

Fig. 2.

Major variations in the genomes of clades A and C in comparison with the EV-D68 Fermon strain. Dashed lines (//) indicate extended genomic regions without variation. Arrows represent the start of the polyprotein ORF.