Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase.
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 degrees C when compared with wild type; however, lower luciferase activities were observed when they were incubated at 39.5 degrees C. In addition, the I251T mutation in the EV71 infectious clone not only reduced viral replication at 39.5 degrees 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.
Kung
Yen-Hua
YH
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.
Huang
Sheng-Wen
SW
Kuo
Pin-Hwa
PH
Kiang
David
D
Ho
Mei-Shang
MS
Liu
Ching-Chung
CC
Yu
Chun-Keung
CK
Su
Ih-Jen
IJ
Wang
Jen-Ren
JR
D000818:Animals; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000502:physiology; D029821:Enterovirus A, Human / Q000235:genetics / Q000472:pathogenicity*; D006232:Hand, Foot and Mouth Disease / Q000821:virology*; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013696:Temperature; D014774:Virulence
D012367:RNA, Viral; D012321:DNA-Directed RNA Polymerases