VIROLOGICAL AND PATHOLOGICAL ANALYSIS OF ENTEROVIRUS 71 ENCEPHALITIS IN THE WESTERN PACIFIC REGION

西太平洋地区肠病毒 71 型脑炎的病毒学和病理学分析

• 批准号: 12576012
• 负责人: SHIMIZU Hiroyuki
• 金额: $ 6.53万
• 依托单位: NATIONAL INSTITUTE OF INFECTIOUS DISEASES
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12576012/
• 关键词: ENTEROVIRUS; ENTEROVIRUS71; HAND, FOOT AND MOUTH DISEASE; ENCEPHALITIS; CNS INFECTION; MOLECULAR EPIDEMIOLOGY; 国際情報交換; マレーシア:中国:タイ:ベトナム; エンテロウイルス感染症

In the late 1990's, large hand, foot and mouth disease (HFMD) outbreaks, mainly caused by enterovirus 71 (EV71), have occurred in the Western Pacific Region, and a number of HFMD cases with severe neurological complications, including fatalities mainly in young children, have been reported in Malaysia and Taiwan. To investigate the virological factors associating to the severity of the diseases, and to monitor the genetic trend of EV71 transmission in the Region, we have conducted molecular epidemiological analyses of the EV71 isolates from cases with HFMD or severe neurological complications in Malaysia, Taiwan, Japan and surrounding areas. The molecular epidemiological analysis of recent EV71 isolates revealed the simultaneous circulation of at least two different genogroups of EV71 (VP1-genogroup B and C), and each genogroup could be divided to more detailed subgenogroups. In collaborating with several enterovirus laboratories in the Region, we introduced disease and laboratory surveillance systems for non-polio enteroviruses including EV71,and described the first virus isolation and identification of EV71 in Viet Nam and Thailand. To analyze the relationship of EV71 that is transmitted in the Region, and to see if there is some relation between the genotype of EV71 and pathogenicity, we have established and improved a cynomolgus monkey model to evaluate the neurovirulence of EV71. The pathogenetic involvement in the monkeys was well correlated with the apparent differences in neurological diseases induced by EV71 in human cases with acute encephalitis. The pathological and virological analyses of the monkeys, which were inoculated with various EV71 isolates, revealed a particular genogroup of EV71 was not directly linked to the severe neurological diseases.

20世纪90年代末，西太平洋地区发生了主要由肠病毒71型（EV71）引起的大规模手足口病暴发，马来西亚和台湾报告了一些伴有严重神经系统并发症的手足口病病例，其中主要是幼儿死亡。为研究与疾病严重程度相关的病毒学因素，并监测EV71病毒在该地区传播的遗传趋势，我们对马来西亚、台湾、日本及周边地区手足口病或严重神经系统并发症病例中分离的EV71病毒进行了分子流行病学分析。近期EV71分离株的分子流行病学分析显示，至少有两个不同的EV71基因组（vp1 -基因组B和基因组C）同时流行，每个基因组可划分为更详细的亚基因组。通过与本区域若干肠道病毒实验室合作，我们引进了包括肠病毒71型在内的非脊髓灰质炎肠道病毒疾病和实验室监测系统，并描述了在越南和泰国首次分离和鉴定出肠病毒71型病毒。为了分析EV71病毒在该地区传播的关系，以及EV71病毒的基因型与致病性之间是否存在一定的关系，我们建立并改进了食蟹猴模型来评价EV71病毒的神经毒力。猴的发病参与与人类急性脑炎病例中EV71引起的神经系统疾病的明显差异密切相关。对接种了各种EV71分离株的猴子进行的病理和病毒学分析显示，EV71的特定基因组与严重的神经系统疾病没有直接联系。

项目成果

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Arita M、Shimizu H、Miyamura T：“病毒蛋白合成活性降低的 1 型脊髓灰质炎病毒突变体的体外和体内表型特征。”J Gen Virol。

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Nagata N、Iwasaki T、Ami Y、Sato Y、Hatano I、Harashima A、Suzaki Y、Yoshii T、Hashikawa T、Sata T、Horiuchi Y、Koike S、Kurata T、Nomoto A：“通过粘膜感染的脊髓灰质炎模型

Nagata N, Iwasaki T, Ami Y, Harashima A, Hatano I, Suzaki Y, Yoshii K, Yoshii T, Nomoto A, Kurata T: "Comparison of neuropathogenicity of poliovirus type 3 in transgenic mice bearing the poliovirus receptor gene and cynomolgus monkeys"Vaccine. 19. 3201-32

Nagata N、Iwasaki T、Ami Y、Harashima A、Hatano I、Suzaki Y、Yoshii K、Yoshii T、Nomoto A、Kurata T：“携带脊髓灰质炎病毒受体基因的转基因小鼠和食蟹猴中脊髓灰质炎病毒 3 型神经致病性的比较”