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

在20世纪90年代后期，主要由肠道病毒71（EV71）引起的手足口病（HFMD）大规模爆发发生在西太平洋区域，并且在马来西亚和台湾已经报告了一些具有严重神经系统并发症的HFMD病例，包括主要在幼儿中的死亡。为探讨与疾病严重程度有关的病毒学因素，以及监察肠病毒71型在区内传播的基因趋势，我们对马来西亚、台湾、日本及邻近地区的手足口病或严重神经系统并发症个案中分离的肠病毒71型进行了分子流行病学分析。近年来的EV71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C）同时存在，并且每个基因组可以划分为更详细的亚基因组。我们与区内多个肠道病毒实验室合作，引进了包括EV 71在内的非脊灰肠道病毒的疾病和实验室监测系统，并介绍了越南和泰国首次分离和鉴定EV 71的情况。为了分析EV71在该地区传播的关系，以及EV71基因型与致病性之间是否存在某种关系，我们建立并改进了一种评价EV71神经毒力的食蟹猴模型。猴子的发病机制与EV71在人类急性脑炎病例中诱导的神经系统疾病的明显差异有很好的相关性。经病理学及病毒学分析后，发现一个特定的EV71基因组与严重的神经系统疾病并无直接关系。

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.