A study of the molecular epidemiology and virulence determinants of enterovirus 71 strains from the Asia-Pacific region

在本研究中，我们的目的是了解自1997年以来在亚太地区幼儿中出现的由肠道病毒71（EV71）引起的严重神经系统疾病流行的原因，并制定疾病预防策略。EV71是一种与脊髓灰质炎病毒密切相关的人类肠道病毒。大多数EV 71感染是轻微的，然而，它们偶尔可能导致严重的疾病，包括死亡率高的脑干脑炎和类似于脊髓灰质炎的急性弛缓性麻痹。自1997年以来，整个亚太地区的EV71流行活动大幅增加，包括1999年在西澳大利亚州珀斯的大规模流行。这些流行病导致许多人死亡和严重神经残疾。鉴于EV71神经系统疾病的严重性和缺乏有效的治疗方法，我们的研究工作需要集中在通过公共卫生监测和疫苗开发来预防。我们的研究主要有两个目的：1。利用分子技术研究EV71在亚太区的起源和演变，并利用这些资料在澳洲和东南亚实施监察。预计监测工作的改进将为即将发生的流行病提供预警。2.了解肠病毒71型毒力的分子基础，特别是病毒引起严重中枢神经系统疾病的能力。本研究将有两个目标：A。鉴定EV71的人细胞受体。本研究的最终目标是通过构建表达EV71人类细胞受体的转基因小鼠，建立EV71脑炎的小动物模型。B.目的构建肠病毒71型感染性cDNA克隆，并通过对该感染性克隆进行诱变，开发遗传上确定的减毒株。将在新生小鼠和人类神经母细胞瘤细胞中测试EV71突变株的复制和毒力。

In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.