Genetic divergence of enterovirus D68 in China and the United States.

Zichun Xiang,Zhengde Xie,Lulu Liu,Jianwei Wang,Lili Ren,Gláucia Paranhos-Baccalà,Yan Xiao

doi:10.1038/srep27800

Abstract

The largest outbreak of human enterovirus 68 (EV-D68) infections associated with severe respiratory illness and neurological complications emerged from the United States in 2014. China reported the circulation of EV-D68 since 2006, but these cases were sporadic and did not display neurological symptoms. Yet viral determinants responsible for the difference in prevalence between China and the U.S. were not clear. We analyzed the genome of 64 reported Chinese EV-D68 strains and found that genogroup replacement has occurred in China since 2006. The six coding mutations (M291T, V341A, T860N, D927N, S1108G and R2005K) associated with neurovirulence reported in American strains were not found in Chinese strains. Moreover, 2014 Chinese strains had a unique R220A mutation in the puff region of VP2 while R220E mutation occurred in other strains. Like other enteroviruses, the loop sequences of the domain X and Y in the 3′-UTR of the Chinese strains are complementary. However, the X loop sequences of the 2014 American strains were not complementary but identical to Y loop sequences. These results indicate that different EV-D68 strains circulated in China and America and the mutations might be responsible for different prevalence. Our findings also provide new evidence for the sequence diversity of EV-D68.

Highlights

Since its discovery in 19621, Enterovirus D68 (EV-D68) has historically been a rarely reported virus linked to respiratory disease
In contrast to the symptoms caused by EV-D68 and the prevalence observed in the United States, none of the cases in China had nervous system dysfunction and no notable outbreak was reported
These 64 EV-D68 sequences were detected from 64 respiratory tract infections (RTIs) cases which distributed in 5 different geographical locations (Beijing, Tianjin, Shanghai, Fujian and Chongqing) indicating a wide distribution of EV-D68 in China

Summary

Introduction

Since its discovery in 19621, Enterovirus D68 (EV-D68) has historically been a rarely reported virus linked to respiratory disease. In contrast to the symptoms caused by EV-D68 and the prevalence observed in the United States, none of the cases in China had nervous system dysfunction and no notable outbreak was reported. EV-D68 is a non-enveloped, single-stranded RNA virus consisting of the genome-linked protein VPg at the 5′end, a highly structured 5′-untranslated region (UTR), a single open reading frame coding for a polyprotein, a 3′-UTR, and a poly (A) tail. The polyprotein is cleaved into 4 viral capsid proteins VP1—VP4 and 7 non-structural proteins involved in protein processing and genome replication, including 2A—2C and 3A—3D by its proteases 2A and 3C14. The 3′-UTR consists of 68 nucleotides and contains a secondary pseudoknot structure that has been implicated in controlling viral RNA synthesis[17]

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