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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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Phylogenetic tree for the VP1 region of enterovirus (EV) 71 isolates in Taiwan between 1998 and 2003 and from surrounding areas between the 1990 s and 2003. Numbers close to the branches are from 1000 bootstrap replicates (%). The two digits at the end of a sequence indicate the year of isolation. Yamagata: Yamagata, Japan; Aus: Australia; SYD: Sydney, Australia; MAA and MA: Malaysia; SAR, Sarawak, Malaysia; Sin: Singapore.
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Figure 5: Phylogenetic tree for the VP1 region of enterovirus (EV) 71 isolates in Taiwan between 1998 and 2003 and from surrounding areas between the 1990 s and 2003. Numbers close to the branches are from 1000 bootstrap replicates (%). The two digits at the end of a sequence indicate the year of isolation. Yamagata: Yamagata, Japan; Aus: Australia; SYD: Sydney, Australia; MAA and MA: Malaysia; SAR, Sarawak, Malaysia; Sin: Singapore.

Mentions: Observations of high viral diversity during epidemic peaks with periodic reductions suggest that either the viruses were maintained in the population and across inter-epidemic intervals or the viruses were imported from other sources as shown in a previous study [13]. Co-circulation of different viral genotypes in extremely low frequencies might be an indication of the former (Table 1). It is possible that these viral strains had been in circulation for some time before the number of cases became large enough to be noted. For example, the viral strains causing the 1999~2000 outbreak were first sampled in September 1999 (1999.75; Figure 1). As the TMRCA estimated for that outbreak ranged 1998.6~1998.9, the above hypothesis suggests that the virus had been circulating for approximately a year before it was sampled. Nevertheless, as EV71 has been rigorously monitored since the 1998 outbreak in Taiwan, it seems unlikely that the virus was able to remain unnoted or did not cause any severe case for almost a year while in circulation. Furthermore, the estimated TMRCAs were all beyond the beginning of the outbreak in which they were sampled (Table 5). To further investigate the phylogenetic origin of different lineages, we acquired EV71 sequences from surrounding areas during the 1990 s to 2003. Phylogenetic relationships of different viral strains is given in Figure 5. Lineage 7 is phylogenetically close to viral strains reported in Malaysia, Australia, and Japan between 1995 and 1999. Lineage 4 from 1998 and 1999 was tightly clustered with the B4 strain from Malaysia in 1997. Lineages 2 and 3 were grouped with viral isolates from Malaysia between 1999 and 2000. Finally, lineage 1 was closest to the B4 strain from Australia in 2000. Figure 5 suggests that EV71 in Taiwan is frequently imported and perhaps moves from and to surrounding areas. Because local viral isolates showed more than 97% identity to their sister group which had been circulating in surrounding areas immediately prior to an outbreak, the importation of viral strains to the local area is the most parsimonious explanation. Both TMRCAs and phylogenetic analyses failed to support the maintenance of viral diversity locally. Alternatively, our results may actually indicate that viral diversities were not maintained in the local area, but were imported from other sources.


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)

Phylogenetic tree for the VP1 region of enterovirus (EV) 71 isolates in Taiwan between 1998 and 2003 and from surrounding areas between the 1990 s and 2003. Numbers close to the branches are from 1000 bootstrap replicates (%). The two digits at the end of a sequence indicate the year of isolation. Yamagata: Yamagata, Japan; Aus: Australia; SYD: Sydney, Australia; MAA and MA: Malaysia; SAR, Sarawak, Malaysia; Sin: Singapore.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Phylogenetic tree for the VP1 region of enterovirus (EV) 71 isolates in Taiwan between 1998 and 2003 and from surrounding areas between the 1990 s and 2003. Numbers close to the branches are from 1000 bootstrap replicates (%). The two digits at the end of a sequence indicate the year of isolation. Yamagata: Yamagata, Japan; Aus: Australia; SYD: Sydney, Australia; MAA and MA: Malaysia; SAR, Sarawak, Malaysia; Sin: Singapore.
Mentions: Observations of high viral diversity during epidemic peaks with periodic reductions suggest that either the viruses were maintained in the population and across inter-epidemic intervals or the viruses were imported from other sources as shown in a previous study [13]. Co-circulation of different viral genotypes in extremely low frequencies might be an indication of the former (Table 1). It is possible that these viral strains had been in circulation for some time before the number of cases became large enough to be noted. For example, the viral strains causing the 1999~2000 outbreak were first sampled in September 1999 (1999.75; Figure 1). As the TMRCA estimated for that outbreak ranged 1998.6~1998.9, the above hypothesis suggests that the virus had been circulating for approximately a year before it was sampled. Nevertheless, as EV71 has been rigorously monitored since the 1998 outbreak in Taiwan, it seems unlikely that the virus was able to remain unnoted or did not cause any severe case for almost a year while in circulation. Furthermore, the estimated TMRCAs were all beyond the beginning of the outbreak in which they were sampled (Table 5). To further investigate the phylogenetic origin of different lineages, we acquired EV71 sequences from surrounding areas during the 1990 s to 2003. Phylogenetic relationships of different viral strains is given in Figure 5. Lineage 7 is phylogenetically close to viral strains reported in Malaysia, Australia, and Japan between 1995 and 1999. Lineage 4 from 1998 and 1999 was tightly clustered with the B4 strain from Malaysia in 1997. Lineages 2 and 3 were grouped with viral isolates from Malaysia between 1999 and 2000. Finally, lineage 1 was closest to the B4 strain from Australia in 2000. Figure 5 suggests that EV71 in Taiwan is frequently imported and perhaps moves from and to surrounding areas. Because local viral isolates showed more than 97% identity to their sister group which had been circulating in surrounding areas immediately prior to an outbreak, the importation of viral strains to the local area is the most parsimonious explanation. Both TMRCAs and phylogenetic analyses failed to support the maintenance of viral diversity locally. Alternatively, our results may actually indicate that viral diversities were not maintained in the local area, but were imported from other sources.

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