title: Molecular evolution and the global reemergence of enterovirus D68 by genome-wide analysis.
abstract: Human enterovirus D68 (EV-D68) was first reported in the United States in 1962; thereafter, a few cases were reported from 1970 to 2005, but 2 outbreaks occurred in the Philippines (2008) and the United States (2014). However, little is known regarding the molecular evolution of this globally reemerging virus due to a lack of whole-genome sequences and analyses. Here, all publically available sequences including 147 full and 1248 partial genomes from GenBank were collected and compared at the clade and subclade level; 11 whole genomes isolated in Taiwan (TW) in 2014 were also added to the database. Phylogenetic trees were constructed to identify a new subclade, B3, and represent clade circulations among strains. Nucleotide sequence identities of the VP1 gene were 94% to 95% based on a comparison of subclade B3 to B1 and B2 and 87% to 91% when comparing A, C, and D. The patterns of clade circulation need to be clarified to improve global monitoring of EV-D68, even though this virus showed lower diversity among clades compared with the common enterovirus EV-71. Notably, severe cases isolated from Taiwan and China in 2014 were found in subclade B3. One severe case from Taiwan occurred in a female patient with underlying angioimmunoblastic T-cell lymphoma, from whom a bronchoalveolar lavage specimen was obtained. Although host factors play a key role in disease severity, we cannot exclude the possibility that EV-D68 may trigger clinical symptoms or death. To further investigate the genetic diversity of EV-D68, we reported 34 amino acid (aa) polymorphisms identified by comparing subclade B3 to B1 and B2. Clade D strains had a 1-aa deletion and a 2-aa insertion in the VP1 gene, and 1 of our TW/2014 strains had a shorter deletion in the 5' untranslated region than a previously reported deletion. In summary, a new subclade, genetic indels, and polymorphisms in global strains were discovered elucidating evolutionary and epidemiological trends of EV-D68, and 11 genomes were added to the database. Virus variants may contribute to disease severity and clinical manifestations, and further studies are needed to investigate the associations between genetic diversity and clinical outcomes.
authors: Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital Department of Medical Biotechnology and Laboratory Science Research Center for Emerging Viral Infections, Chang Gung University Department of Pediatrics, Linkou Chang Gung Memorial Hospital College of Medicine, Chang Gung University Department of Respiratory Therapy Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital Department of Respiratory Therapy Department of Pulmonary and Critical Care Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Yu-Nong
authors: YN
authors: Gong
authors: Shu-Li
authors: SL
authors: Yang
authors: Shin-Ru
authors: SR
authors: Shih
authors: Yhu-Chering
authors: YC
authors: Huang
authors: Pi-Yueh
authors: PY
authors: Chang
authors: Chung-Guei
authors: CG
authors: Huang
authors: Kuo-Chin
authors: KC
authors: Kao
authors: Han-Chung
authors: HC
authors: Hu
authors: Yi-Chun
authors: YC
authors: Liu
authors: Kuo-Chien
authors: KC
authors: Tsao
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D030016:Enterovirus D, Human / Q000235:genetics*; D004769:Enterovirus Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D055106:Genome-Wide Association Study; D014943:Global Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D013624:Taiwan / Q000453:epidemiology
chemical_list: D012367:RNA, Viral