title: Genetic characterization of enterovirus 71 isolated from patients with severe disease by comparative analysis of complete genomes.
abstract: Enterovirus 71 (EV71) which causes mild illness in children is also associated with severe neurological complications. This study analyzed the complete genomes of EV71 strains derived from mild and severe diseases in order to determine whether the differences of EV71 genomes were responsible for different clinical presentations. Compared to complete genomes of EV71 strains derived from mild cases (less virulent strains), nucleotide differences in EV71 strains isolated from severe cases (more virulent strains) were observed primarily in the internal ribosomal entry site (IRES) of the 5'-untranslated region (UTR), which is vital for the cap-independent translation of viral proteins. In the protein-coding region, an E-Q substitution at amino acid position 145 of structural protein VP1 that occurred in more than one of more virulent strains was observed. This site is known to be related functionally to receptor binding and virulence in mice. Overall, strains (Group III) isolated from patients with fatal or severe sequelae outcomes had greater sequence substitutions in the 5'-UTR and/or protein-coding region and exhibited a relatively low-average homology to less virulent strains across the entire genome, indicating the possibility of significant genomic diversity in the most virulent EV71 strains. Further studies of EV71 pathogenesis should examine the significance of genomic diversity and the effects of multiple mutations in a viral population.
authors.affiliation: Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shih-Cheng
authors.initials: SC
authors.lastname: Chang
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Li
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Chen
authors.forename: Kuo-Chien
authors.initials: KC
authors.lastname: Tsao
authors.forename: Chung-Guei
authors.initials: CG
authors.lastname: Huang
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Chiu
authors.forename: Chen-Yen
authors.initials: CY
authors.lastname: Kuo
authors.forename: Kun-Nan
authors.initials: KN
authors.lastname: Tsai
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
mesh_terms: D020121:5' Untranslated Regions; D019943:Amino Acid Substitution; D029821:Enterovirus A, Human / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000473:pathology* / Q000821:virology*; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral; D037521:Virulence Factors