title: A single nucleotide in stem loop II of 5'-untranslated region contributes to virulence of enterovirus 71 in mice.
abstract: BACKGROUND
  Enterovirus 71 (EV71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored.
  
  
  RESULTS
  In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL) II of 237 5'-untranslated region (UTR) visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo.
  
  
  CONCLUSIONS
  These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates.
authors: The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors: Ming-Te
authors: MT
authors: Yeh
authors: Shainn-Wei
authors: SW
authors: Wang
authors: Chun-Keung
authors: CK
authors: Yu
authors: Kuei-Hsiang
authors: KH
authors: Lin
authors: Huan-Yao
authors: HY
authors: Lei
authors: Ih-Jen
authors: IJ
authors: Su
authors: Jen-Ren
authors: JR
authors: Wang
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004770:Enterovirus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000235:genetics* / Q000401:mortality; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D015996:Survival Rate; D014774:Virulence; D014779:Virus Replication
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral