Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics
Dengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. Recent analyses suggest that antigenic heterogeneity may exist within each serotype, but its source, extent and impact remain unclear. Here, we construct a sequence-b...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/42496 |
| _version_ | 1797851628017025024 |
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| author | Sidney M Bell Leah Katzelnick Trevor Bedford |
| author_facet | Sidney M Bell Leah Katzelnick Trevor Bedford |
| author_sort | Sidney M Bell |
| collection | DOAJ |
| description | Dengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. Recent analyses suggest that antigenic heterogeneity may exist within each serotype, but its source, extent and impact remain unclear. Here, we construct a sequence-based model to directly map antigenic change to underlying genetic divergence. We identify 49 specific substitutions and four colinear substitution clusters that robustly predict dengue antigenic relationships. We report moderate antigenic diversity within each serotype, resulting in genotype-specific patterns of heterotypic cross-neutralization. We also quantify the impact of antigenic variation on real-world DENV population dynamics, and find that serotype-level antigenic fitness is a dominant driver of dengue clade turnover. These results provide a more nuanced understanding of the relationship between dengue genetic and antigenic evolution, and quantify the effect of antigenic fitness on dengue evolutionary dynamics. |
| first_indexed | 2024-04-09T19:19:46Z |
| format | Article |
| id | doaj.art-23411d1cd7a14a488b45d25127f0fef5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T19:19:46Z |
| publishDate | 2019-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-23411d1cd7a14a488b45d25127f0fef52023-04-05T14:12:40ZengeLife Sciences Publications LtdeLife2050-084X2019-08-01810.7554/eLife.42496Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamicsSidney M Bell0https://orcid.org/0000-0003-1933-6033Leah Katzelnick1Trevor Bedford2https://orcid.org/0000-0002-4039-5794Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Molecular and Cell Biology Program, University of Washington, Seattle, United StatesDivision of Infectious Diseases and Vaccinology, University of California, Berkeley, Berkeley, United States; Department of Biology, University of Florida, Gainesville, United StatesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesDengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. Recent analyses suggest that antigenic heterogeneity may exist within each serotype, but its source, extent and impact remain unclear. Here, we construct a sequence-based model to directly map antigenic change to underlying genetic divergence. We identify 49 specific substitutions and four colinear substitution clusters that robustly predict dengue antigenic relationships. We report moderate antigenic diversity within each serotype, resulting in genotype-specific patterns of heterotypic cross-neutralization. We also quantify the impact of antigenic variation on real-world DENV population dynamics, and find that serotype-level antigenic fitness is a dominant driver of dengue clade turnover. These results provide a more nuanced understanding of the relationship between dengue genetic and antigenic evolution, and quantify the effect of antigenic fitness on dengue evolutionary dynamics.https://elifesciences.org/articles/42496dengueantigenic evolutionviral fitness |
| spellingShingle | Sidney M Bell Leah Katzelnick Trevor Bedford Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics eLife dengue antigenic evolution viral fitness |
| title | Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics |
| title_full | Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics |
| title_fullStr | Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics |
| title_full_unstemmed | Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics |
| title_short | Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics |
| title_sort | dengue genetic divergence generates within serotype antigenic variation but serotypes dominate evolutionary dynamics |
| topic | dengue antigenic evolution viral fitness |
| url | https://elifesciences.org/articles/42496 |
| work_keys_str_mv | AT sidneymbell denguegeneticdivergencegenerateswithinserotypeantigenicvariationbutserotypesdominateevolutionarydynamics AT leahkatzelnick denguegeneticdivergencegenerateswithinserotypeantigenicvariationbutserotypesdominateevolutionarydynamics AT trevorbedford denguegeneticdivergencegenerateswithinserotypeantigenicvariationbutserotypesdominateevolutionarydynamics |