Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Blackburn Building D06, Sydney NSW 2006, Australia.
J Gen Virol. 2012 Sep;93(Pt 9):1935-1940. doi: 10.1099/vir.0.043893-0. Epub 2012 May 30.
We modified the capsid protein of a human enterovirus 71 (HEV71) belonging to subgenogroup C4 (HEV71-C4) to generate a mouse virulent strain, based on the genetic information derived from our previous subgenogroup B3 mouse-adapted virus. Infectious clone-derived mutant virus populations containing the capsid protein mutations VP1-Q145E and VP1-Q145G were generated by site-directed mutagenesis of an infectious clone of a subgenogroup C4 strain. Viruses expressing the VP1-Q145E were virulent in 5-day-old BALB/c mice with 100 % mortality rate observed. Skeletal muscle appears to be the primary site of replication of this virus with limb muscle showing severe myositis. Virus was also isolated from spleen, liver, heart and brain of infected mice. This study demonstrates that introducing a key mutation into the HEV71 VP1 capsid protein is able to generate a mouse virulent HEV71 strain from a different genogroup as well as providing an alternative strategy for the generation of mouse virulent HEV71.
我们基于源自先前的 B3 亚组适应小鼠的病毒的遗传信息，对属于 C4 亚组的人类肠道病毒 71（HEV71）衣壳蛋白进行了修饰，以生成一种小鼠毒力株。通过对 C4 亚组株的感染性克隆进行定点诱变，产生了含有衣壳蛋白突变 VP1-Q145E 和 VP1-Q145G 的感染性克隆衍生的突变病毒群。表达 VP1-Q145E 的病毒在 5 日龄 BALB/c 小鼠中具有毒力，观察到 100%的死亡率。骨骼肌似乎是该病毒的主要复制部位，四肢肌肉出现严重的肌炎。病毒也从感染小鼠的脾脏、肝脏、心脏和大脑中分离出来。这项研究表明，将关键突变引入 HEV71 VP1 衣壳蛋白能够从不同的基因群中生成一种小鼠毒力的 HEV71 株，并为生成小鼠毒力的 HEV71 提供了另一种策略。
