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

20世纪90年代末，S在西太平洋地区爆发了以肠道病毒71型为主的手足口病暴发，马来西亚和台湾报告了一些具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。为探讨与疾病严重程度相关的病毒学因素，并监测该地区EV71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的EV71分离株进行了分子流行病学分析。对新近分离的EV71分离株的分子流行病学分析显示，至少有两个不同的EV71基因群(VP1-B和C基因群)同时传播，每个基因群可以划分为更详细的亚基因组。在与该地区几个肠道病毒实验室的合作中，我们引入了包括EV71型在内的非脊髓灰质炎肠道病毒的疾病和实验室监测系统，并描述了越南和泰国首次分离和鉴定EV71型病毒。为了分析EV71在该地区传播的关系，以及EV71基因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的神经毒力。猴的致病过程与EV71在人类急性脑炎病例中引起的神经系统疾病的明显差异密切相关。对接种了不同EV71分离株的猴子进行的病理学和病毒学分析显示，EV71的一个特定基因组与严重的神经系统疾病没有直接联系。

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.