A single nucleotide in stem loop II of 5′-untranslated region contributes to virulence of Enterovirus 71 in mice

Ming Te Yeh, Shainn Wei Wang, Chun Keung Yu, Kuei Hsiang Lin, Huan Yao Lei, Ih Jen Su, Jen Ren Wang

Research output: Contribution to journalArticle

30 Citations (Scopus)

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. Principal Findings: 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.

Original languageEnglish
Article numbere27082
JournalPloS one
Volume6
Issue number10
DOIs
Publication statusPublished - 2011 Nov 1

Fingerprint

Enterovirus
5' Untranslated Regions
5' untranslated regions
Virulence
virulence
Nucleotides
nucleotides
stems
mice
Viruses
Cytosine Nucleotides
Replicon
translation (genetics)
Uridine
replicon
viruses
Plasmids
uridine
cytosine
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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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. Principal Findings: 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.",
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A single nucleotide in stem loop II of 5′-untranslated region contributes to virulence of Enterovirus 71 in mice. / Yeh, Ming Te; Wang, Shainn Wei; Yu, Chun Keung; Lin, Kuei Hsiang; Lei, Huan Yao; Su, Ih Jen; Wang, Jen Ren.

In: PloS one, Vol. 6, No. 10, e27082, 01.11.2011.

Research output: Contribution to journalArticle

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AU - Wang, Shainn Wei

AU - Yu, Chun Keung

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AU - Lei, Huan Yao

AU - Su, Ih Jen

AU - Wang, Jen Ren

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AB - 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. Principal Findings: 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.

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