AbuBakar, S.; Chan, Y.F.; Lam, S.K.; Ho, M.; Wang, J.R.; Shih, S.R. (2000) Outbreaks of enterovirus 71 infection. New England Journal of Medicine, 342 (5). pp. 355-356.
The outbreak of enterovirus 71 infection in Taiwan, reported by Ho et al. (Sept. 23 issue), 1 occurred almost a year after the outbreak in Malaysia. Though both outbreaks occurred in Asia and both involved large numbers of deaths, it was not known whether the two outbreaks were related. We studied the nucleotide sequence and secondary RNA structure of some of the isolates, using the sequence of the 5' untranslated region (UTR). Enterovirus 71 isolates from patients in Singapore (seven isolates), Taiwan (two isolates), and Japan (one isolate) were examined and compared with those previously reported in Malaysia 2,3 or with sequences deposited in GenBank. A phylogenetic tree that we constructed using the aligned 5' UTR sequences revealed at least two major clusters of enterovirus 71 isolates. Cluster 1 included the isolate from Japan and six of the seven isolates from Singapore, together with isolates found predominantly in Malaysia during the 1997 outbreak. The isolates in this cluster had at least 89 percent sequence homology with enterovirus 71 MS isolates. The isolates in cluster 1 formed two subclusters. The isolate from Japan and five of the six isolates from Singapore were clustered with isolates from the Malaysian peninsula, forming one subcluster, and the remaining isolates, which included others from the Malaysian peninsula, Sarawak, and Singapore, formed the other subcluster. Three other isolates examined, one from Singapore and two from Taiwan, were in cluster 2, which consisted mostly of isolates from the 1998 outbreak in Taiwan. Cluster 2 also had two subclusters, with all the isolates from Taiwan, including the two sequenced in this study, in one subcluster and the remaining isolates from the Malaysian peninsula and Singapore in the other. The isolates in these two subclusters had at least 97 percent homology with each other and approximately 85 percent homology with the coxsackievirus A9 5' UTR sequence rather than with the enterovirus 71 MS group, which contained the other enterovirus 71 strains found predominantly in Malaysia and Singapore. A comparison of the 5' UTR secondary RNA structure, which has been associated with the degree of virulence, in the cluster 2 isolates revealed no significant differences in the structure of the three domains within the 5' UTR sequence. These findings suggest that the 5' UTR features of the enterovirus 71 strains from the Taiwanese outbreak were almost identical to those of the coxsackievirus A9â��like strains isolated previously in the Malaysian peninsula. 3 Because of these similarities and the high frequency of travel between Malaysia and Taiwan, it is tempting to speculate that the predominant enterovirus 71 strains in the Taiwanese outbreak may have been accidental imports.
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