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Inferring nonneutral evolution from contrasting patterns of polymorphisms and divergences in different protein coding regions of enterovirus 71 circulating in Taiwan during 1998-2003.

Wang HY, Tsao KC, Hsieh CH, Huang LM, Lin TY, Chen GW, Shih SR, Chang LY - BMC Evol. Biol. (2010)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.

ABSTRACT

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.

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Identification of recombined regions between different species of human enterovirus (HEV)-A. The upper panel shows the genomic structure of enterovirus (EV) 71. The results from a bootscan analysis indicated the likelihood of recombination of (a) EV71-C1+C2, (b) EV71-C4, and (c) CA16-like with their potential parental species/genotype. All species listed in "Methods" were used, but only species or groups with > 50% phylogenetic relatedness are shown. EV71-C1+C2 (DQ452074, AF119795, and AF176044); EV71-C4 (AF302996 and AY465356); CA16-like (AF177911 and AY790926); and EV71-B (U22522, AF352027, and AF316321).
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Figure 3: Identification of recombined regions between different species of human enterovirus (HEV)-A. The upper panel shows the genomic structure of enterovirus (EV) 71. The results from a bootscan analysis indicated the likelihood of recombination of (a) EV71-C1+C2, (b) EV71-C4, and (c) CA16-like with their potential parental species/genotype. All species listed in "Methods" were used, but only species or groups with > 50% phylogenetic relatedness are shown. EV71-C1+C2 (DQ452074, AF119795, and AF176044); EV71-C4 (AF302996 and AY465356); CA16-like (AF177911 and AY790926); and EV71-B (U22522, AF352027, and AF316321).

Mentions: Inconsistent phylogenies derived from different genomic regions imply frequent recombinations between different species of human enterovirus species (HEV)-A as previously noted [23]. In Figure 2, lineages 5 and 6 clustered tightly with CA8 in the 3C and 5'UTR regions, but they were recognized as EV71 genotype C (C1 and C2, respectively) based on the VP1 sequences. It is likely that genotypes C1 and C2 were generated by acquiring the structural domain of ancestral EV71. We further used the bootscan program to detect the region of possible recombination. When EV71-C1 and -C2 were compared against different viruses of HEV-A, two recombination events between CA8 and EV71 (either genotype A or B or both combined) in the 5'UTR (within nucleotide 400~600) and 2A regions (within nucleotide 3400~3600) were clearly demonstrated (Figure 3a). Other examples of sequence acquisition were provided by the analyses of the EV71-C4 (Figure 3b) and CA16-like (Figure 3c) viral strains, the structural domains of which only resembled those of EV71-C1+C2 and CA16, respectively. Interestingly, in the above three cases, the break points of recombination were all located at the 3' end of the 5'UTR and 2A regions which neatly covers the entire structural (= P1) domain of the enterovirus.


Inferring nonneutral evolution from contrasting patterns of polymorphisms and divergences in different protein coding regions of enterovirus 71 circulating in Taiwan during 1998-2003.

Wang HY, Tsao KC, Hsieh CH, Huang LM, Lin TY, Chen GW, Shih SR, Chang LY - BMC Evol. Biol. (2010)

Identification of recombined regions between different species of human enterovirus (HEV)-A. The upper panel shows the genomic structure of enterovirus (EV) 71. The results from a bootscan analysis indicated the likelihood of recombination of (a) EV71-C1+C2, (b) EV71-C4, and (c) CA16-like with their potential parental species/genotype. All species listed in "Methods" were used, but only species or groups with > 50% phylogenetic relatedness are shown. EV71-C1+C2 (DQ452074, AF119795, and AF176044); EV71-C4 (AF302996 and AY465356); CA16-like (AF177911 and AY790926); and EV71-B (U22522, AF352027, and AF316321).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2958165&req=5

Figure 3: Identification of recombined regions between different species of human enterovirus (HEV)-A. The upper panel shows the genomic structure of enterovirus (EV) 71. The results from a bootscan analysis indicated the likelihood of recombination of (a) EV71-C1+C2, (b) EV71-C4, and (c) CA16-like with their potential parental species/genotype. All species listed in "Methods" were used, but only species or groups with > 50% phylogenetic relatedness are shown. EV71-C1+C2 (DQ452074, AF119795, and AF176044); EV71-C4 (AF302996 and AY465356); CA16-like (AF177911 and AY790926); and EV71-B (U22522, AF352027, and AF316321).
Mentions: Inconsistent phylogenies derived from different genomic regions imply frequent recombinations between different species of human enterovirus species (HEV)-A as previously noted [23]. In Figure 2, lineages 5 and 6 clustered tightly with CA8 in the 3C and 5'UTR regions, but they were recognized as EV71 genotype C (C1 and C2, respectively) based on the VP1 sequences. It is likely that genotypes C1 and C2 were generated by acquiring the structural domain of ancestral EV71. We further used the bootscan program to detect the region of possible recombination. When EV71-C1 and -C2 were compared against different viruses of HEV-A, two recombination events between CA8 and EV71 (either genotype A or B or both combined) in the 5'UTR (within nucleotide 400~600) and 2A regions (within nucleotide 3400~3600) were clearly demonstrated (Figure 3a). Other examples of sequence acquisition were provided by the analyses of the EV71-C4 (Figure 3b) and CA16-like (Figure 3c) viral strains, the structural domains of which only resembled those of EV71-C1+C2 and CA16, respectively. Interestingly, in the above three cases, the break points of recombination were all located at the 3' end of the 5'UTR and 2A regions which neatly covers the entire structural (= P1) domain of the enterovirus.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus