First Report of a Fatal Case Associated with EV-D68 Infection in Hong Kong and Emergence of an Interclade Recombinant in China Revealed by Genome Analysis

Abstract

A fatal case associated with enterovirus D68 (EV-D68) infection affecting a 10-year-old boy was reported in Hong Kong in 2014. To examine if a new strain has emerged in Hong Kong, we sequenced the partial genome of the EV-D68 strain identified from the fatal case and the complete VP1, and partial 5′UTR and 2C sequences of nine additional EV-D68 strains isolated from patients in Hong Kong. Sequence analysis indicated that a cluster of strains including the previously recognized A2 strains should belong to a separate clade, clade D, which is further divided into subclades D1 and D2. Among the 10 EV-D68 strains, 7 (including the fatal case) belonged to the previously described, newly emerged subclade B3, 2 belonged to subclade B1, and 1 belonged to subclade D1. Three EV-D68 strains, each from subclades B1, B3, and D1, were selected for complete genome sequencing and recombination analysis. While no evidence of recombination was noted among local strains, interclade recombination was identified in subclade D2 strains detected in mainland China in 2008 with VP2 acquired from clade A. This study supports the reclassification of subclade A2 into clade D1, and demonstrates interclade recombination between clades A and D2 in EV-D68 strains from China.

Contemporary Circulating Enterovirus D68 Strains Have Acquired the Capacity for Viral Entry and Replication in Human Neuronal Cells

“…Here we report on the differential infectivity between various contemporary and historical EV-D68 strains in SH-SY5Y as measured by viral replication, cell viability, CPE, and immunofluorescence. The clade specificity of neuropathogenesis previously reported ( 10 , 22 , 26 – 28 , 33 , 34 ) between contemporary and historical strains is observed in the neurotropism in SH-SY5Y cells ( Fig. 5 ).…”

“…EV-D68 has continued to evolve since the 2014 outbreak, which is unsurprising as mutation and recombination are known to occur in enteroviruses ( 23 – 25 ). Sequence analysis has led to the classification of a new clade, D (a subclade of A) ( 26 , 27 ), and a new subclade, B3, has emerged and quickly expanded ( 26 , 28 , 29 ). Neurological symptoms have been associated with the novel B3 clade in Sweden ( 30 ), The Netherlands ( 31 ), Taiwan ( 32 ), Italy ( 33 ), and the United States ( 34 ), which experienced another AFM outbreak during the 2016 enterovirus season (summer and fall), with a total of 149 confirmed cases ( 2 ).…”

An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms

“…The extended primer grip of the poliovirus polymerase highlighted by the work presented herein is conserved across picornavirus species groups and likely mediates genetic exchange between viruses in nature. Intraspecies recombination is well documented for enterovirus species A (39, 67), species B (38, 68), species C (36) and species D viruses (69, 70), as well as rhinovirus species groups (37, 71), parechoviruses (35) and non-human enteroviruses (41). cVDPVs arise, in part, due to improved fitness from genetic exchange with non-polio group C enteroviruses in the field (46–50).…”

Molecular Research on Emerging Viruses: Evolution, Diagnostics, Pathogenesis, and Therapeutics

“…In particular, enterovirus-D68 has emerged in recent years in various countries and is increasingly recognized as an important respiratory pathogen in the young and immunocompromised. In the article by Yip et al, the first fatal case of EV-D68 infection and genetic diversity of EV-D68 strains in Hong Kong were described [ 14 ]. The study also found a newly emerged subclade B3 and an interclade recombination between clade A and D2 strains in China.…”