Kung Yen-Hua, Huang Sheng-Wen, Kuo Pin-Hwa, Kiang David, Ho Mei-Shang, Liu Ching-Chung, Yu Chun-Keung, Su Ih-Jen, Wang Jen-Ren
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.
Virology. 2010 Jan 5;396(1):1-9. doi: 10.1016/j.virol.2009.10.017. Epub 2009 Nov 10.
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.
1998年，台湾地区发生肠道病毒71型（EV71）疫情，导致78人死亡；然而，EV71致病性的分子基础仍知之甚少。对EV71临床分离株3D聚合酶推导的氨基酸序列进行比较，发现1986年和1998年疫情暴发的病毒存在T251V或T251I替换。一个EV71复制子系统显示，与野生型相比，引入I251T突变在35℃时不影响荧光素酶活性；然而，当在39.5℃孵育时，观察到荧光素酶活性较低。此外，EV71感染性克隆中的I251T突变不仅在体外39.5℃时降低了病毒复制，而且在腹腔感染模型中降低了小鼠适应性毒株MP4在新生小鼠中的毒力。因此，这些结果表明，251位的苏氨酸导致了EV71的温度敏感性表型，这可能有助于循环毒株的减毒。
