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Reemergence of enterovirus 71 in 2008 in taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008.

ABSTRACT: In recent years, enterovirus 71 (EV71) has been a cause of numerous outbreaks of hand-foot-and-mouth disease, with severe neurological complications in the Asia-Pacific region. The reemergence in Taiwan of EV71 genotype B5 in 2008 resulted in the largest outbreak of EV71 in Taiwan in the past 11 years. Phylogenetic analyses indicated that dominant genotype changes from B to C or C to B occurred at least three times between 1986 and 2008. Furthermore, antigenic cartography of EV71 by using neutralization tests revealed that the reemerging EV71 genotype B5 strains formed a separate cluster which was antigenically distinct from the B4 and C genotypes. Moreover, analyses of full-length genomic sequences of EV71 circulating in Taiwan during this period showed the occurrence of intra- and interserotypic recombination. Therefore, continuous surveillance of EV71 including the monitoring of genetic evolution and antigenic changes is recommended and may contribute to the development of a vaccine for EV71.

SUBMITTER: Huang SW

PROVIDER: S-EPMC2772620 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Reemergence of enterovirus 71 in 2008 in taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008.

Huang Sheng-Wen SW Hsu Yun-Wei YW Smith Derek J DJ Kiang David D Tsai Huey-Pin HP Lin Kuei-Hsiang KH Wang Shih-Min SM Liu Ching-Chung CC Su Ih-Jen IJ Wang Jen-Ren JR

Journal of clinical microbiology 20090923 11

In recent years, enterovirus 71 (EV71) has been a cause of numerous outbreaks of hand-foot-and-mouth disease, with severe neurological complications in the Asia-Pacific region. The reemergence in Taiwan of EV71 genotype B5 in 2008 resulted in the largest outbreak of EV71 in Taiwan in the past 11 years. Phylogenetic analyses indicated that dominant genotype changes from B to C or C to B occurred at least three times between 1986 and 2008. Furthermore, antigenic cartography of EV71 by using neutra ...[more]

PMID: 19776232

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Project description:BackgroundSince 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD). Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71) belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high.Methodology/principal findingsTo gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010.ConclusionsEV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate persistently among the Chinese population.

Project description:BACKGROUND: Enterovirus (EV) 71 is one of the common causative agents for hand, foot, and, mouth disease (HFMD). In recent years, the virus caused several outbreaks with high numbers of deaths and severe neurological complications. Despite the importance of these epidemics, several aspects of the evolutionary and epidemiological dynamics, including viral nucleotide variations within and between different outbreaks, rates of change in immune-related structural regions vs. non-structural regions, and forces driving the evolution of EV71, are still not clear. RESULTS: We sequenced four genomic segments, i.e., the 5' untranslated region (UTR), VP1, 2A, and 3C, of 395 EV71 viral strains collected from 1998 to 2003 in Taiwan. The phylogenies derived from different genomic segments revealed different relationships, indicating frequent sequence recombinations as previously noted. In addition to simple recombinations, exchanges of the P1 domain between different species/genotypes of human enterovirus species (HEV)-A were repeatedly observed. Contrasting patterns of polymorphisms and divergences were found between structural (VP1) and non-structural segments (2A and 3C), i.e., the former was less polymorphic within an outbreak but more divergent between different HEV-A species than the latter two. Our computer simulation demonstrated a significant excess of amino acid replacements in the VP1 region implying its possible role in adaptive evolution. Between different epidemic seasons, we observed high viral diversity in the epidemic peaks followed by severe reductions in diversity. Viruses sampled in successive epidemic seasons were not sister to each other, indicating that the annual outbreaks of EV71 were due to genetically distinct lineages. CONCLUSIONS: Based on observations of accelerated amino acid changes and frequent exchanges of the P1 domain, we propose that positive selection and subsequent frequent domain shuffling are two important mechanisms for generating new genotypes of HEV-A. Our viral dynamics analysis suggested that the importation of EV71 from surrounding areas likely contributes to local EV71 outbreaks.

Dataset Information

Reemergence of enterovirus 71 in 2008 in taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008.

Publications

Reemergence of enterovirus 71 in 2008 in taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008.

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