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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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Related in: MedlinePlus

Occurrences (left y-axis) and temporal changes in the relative genetic diversity (right y-axis) of major enterovirus (EV) 71 lineages each month. Occurrences of major lineages, lineages 1~4 (EV71-B4) and lineage 7 (EV71-C2), are shown as a bar plot. The lines represent median (red line) and 95% highest posterior densities (HPDs; gray line) of the Bayesian skyline plot derived from VP1 of lineages 1~3.
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Figure 1: Occurrences (left y-axis) and temporal changes in the relative genetic diversity (right y-axis) of major enterovirus (EV) 71 lineages each month. Occurrences of major lineages, lineages 1~4 (EV71-B4) and lineage 7 (EV71-C2), are shown as a bar plot. The lines represent median (red line) and 95% highest posterior densities (HPDs; gray line) of the Bayesian skyline plot derived from VP1 of lineages 1~3.

Mentions: Within each segment, the homoplasy test [20], GENECONV [21], and GARD [22] failed to identify any recombination event for either within- or between-genotype comparisons. In order to test for possible recombinations between sequenced regions, we combined the four segments for further analysis. The concatenated dataset was divided into 10 lineages at the 1% level of divergence. According to sequence similarities of VP1, genotype B4 included four lineages (1 to 4); genotype C contained three lineages, i.e., lineages 5 (genotype C4), 6 (C1), and 7 (C2); and CA16-like had two lineages, 8 and 9. The last lineage which contained only one viral isolate, TW-2051-98, was identified as a recombinant of lineages 4 and 7 (p < 0.01; KH test after GARD and homoplasy test) with the breaking point located between 2A and 3C, and thus it was excluded from further analysis (Additional file 2, Figure S1). No other recombination was detected within any lineage. The occurrences of major lineages from 1998 to 2003 are given in Figure 1. With the exception of 2000, EV71 outbreaks in each season contained only one major lineage. In addition, each lineage was unique to that sampled season with no recurrence in later outbreaks. For example, lineage 4 was from 1998 and 1999, lineages 2 and 3 contained viral strains recovered mainly from 2000, and lineage 1 included viruses from 2001 to 2003.


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)

Occurrences (left y-axis) and temporal changes in the relative genetic diversity (right y-axis) of major enterovirus (EV) 71 lineages each month. Occurrences of major lineages, lineages 1~4 (EV71-B4) and lineage 7 (EV71-C2), are shown as a bar plot. The lines represent median (red line) and 95% highest posterior densities (HPDs; gray line) of the Bayesian skyline plot derived from VP1 of lineages 1~3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Occurrences (left y-axis) and temporal changes in the relative genetic diversity (right y-axis) of major enterovirus (EV) 71 lineages each month. Occurrences of major lineages, lineages 1~4 (EV71-B4) and lineage 7 (EV71-C2), are shown as a bar plot. The lines represent median (red line) and 95% highest posterior densities (HPDs; gray line) of the Bayesian skyline plot derived from VP1 of lineages 1~3.
Mentions: Within each segment, the homoplasy test [20], GENECONV [21], and GARD [22] failed to identify any recombination event for either within- or between-genotype comparisons. In order to test for possible recombinations between sequenced regions, we combined the four segments for further analysis. The concatenated dataset was divided into 10 lineages at the 1% level of divergence. According to sequence similarities of VP1, genotype B4 included four lineages (1 to 4); genotype C contained three lineages, i.e., lineages 5 (genotype C4), 6 (C1), and 7 (C2); and CA16-like had two lineages, 8 and 9. The last lineage which contained only one viral isolate, TW-2051-98, was identified as a recombinant of lineages 4 and 7 (p < 0.01; KH test after GARD and homoplasy test) with the breaking point located between 2A and 3C, and thus it was excluded from further analysis (Additional file 2, Figure S1). No other recombination was detected within any lineage. The occurrences of major lineages from 1998 to 2003 are given in Figure 1. With the exception of 2000, EV71 outbreaks in each season contained only one major lineage. In addition, each lineage was unique to that sampled season with no recurrence in later outbreaks. For example, lineage 4 was from 1998 and 1999, lineages 2 and 3 contained viral strains recovered mainly from 2000, and lineage 1 included viruses from 2001 to 2003.

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