Elsevier

Virology

Volume 396, Issue 1, 5 January 2010, Pages 1-9
Virology

Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase

https://doi.org/10.1016/j.virol.2009.10.017Get rights and content
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Abstract

In 1998, an enterovirus 71 (EV71) epidemic in Taiwan resulted in 78 deaths; however, the molecular basis of EV71 pathogenicity remains poorly understood. Comparison of the deduced amino acid sequences in 3D polymerases of EV71clinical isolates showed the T251V or T251I substitution from 1986 and 1998 outbreaks. An EV71 replicon system showed that introducing an I251T mutation did not affect luciferase activities at 35 °C when compared with wild type; however, lower luciferase activities were observed when they were incubated at 39.5 °C. In addition, the I251T mutation in the EV71 infectious clone not only reduced viral replication at 39.5 °C in vitro but also decreased the virulence of the mouse adaptive strain MP4 in neonatal mice in an i.p. infection model. Therefore, these results suggested that the threonine at position 251 results in a temperature sensitivity phenotype of EV71 which may contribute to the attenuation of circulating strains.

Abbreviations

EV71
Enterovirus 71
HFMD
hand foot and mouth disease
UTR
untranslated region
TR
temperature resistant
TS
temperature sensitive

Keywords

Enterovirus 71
RNA polymerase
Temperature susceptibility

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