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PLoS One. 2011;6(11):e27082. doi: 10.1371/journal.pone.0027082. Epub 2011 Nov 1.

A single nucleotide in stem loop II of 5'-untranslated region contributes to virulence of enterovirus 71 in mice.

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  • 1The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.

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.

PMID:
22069490
PMCID:
PMC3206083
DOI:
10.1371/journal.pone.0027082
[PubMed - indexed for MEDLINE]
Free PMC Article
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