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

亚太地区肠道病毒71株的分子流行病学和毒力决定因素研究

• 批准号: nhmrc : 254569
• 负责人: Darren Shafren
• 金额: $ 19.09万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/study-molecular-epidemiology-pacific-region/95697
• 关键词: study; molecular; epidemiology; virulence; determinants

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.

在本研究中，我们旨在了解自1997年以来亚太地区幼儿中肠道病毒71型（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EV71感染都很轻微，但有时可能会导致严重疾病，包括死亡率很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EV71流行活动大幅增加，其中包括1999年在西澳大利亚州珀斯的大流行。这些流行病导致许多人死亡和严重神经功能障碍的病例。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侧重于通过公共卫生监测和疫苗开发进行预防。我们研究的主要目的有两个： 1. 利用分子技术研究亚太地区 EV71 的起源和演变，并利用这些信息在澳大利亚和东南亚实施监测。预计改进的监测将为即将发生的流行病提供早期预警。 2. 了解EV71毒力的分子基础，重点是病毒引起中枢神经系统严重疾病的能力。这项研究有两个目标：鉴定 EV71 的人类细胞受体。这项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来开发 EV71 脑炎小动物模型。 b.构建 EV71 感染性 cDNA 克隆，并通过感染性克隆的诱变开发遗传定义的减毒株。 EV71 突变株将在新生小鼠和人类神经母细胞瘤细胞中进行复制和毒力测试。