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Mosquitoes Put the Brake on Arbovirus Evolution: Experimental Evolution Reveals Slower Mutation Accumulation in Mosquito Than Vertebrate Cells
Open accessAbstract
Like other arthropod-borne viruses (arboviruses), mosquito-borne dengue virus (DENV) is maintained in an alternating cycle of replication in arthropod and vertebrate hosts. The trade-off hypothesis suggests that this alternation constrains DENV evolution because a fitness increase in one host usually diminishes fitness in the other. Moreover, the hypothesis predicts that releasing DENV from host alternation should facilitate adaptation. To test this prediction, DENV was serially passaged in either a single human cell line (Huh-7), a single mosquito cell line (C6/36), or in alternating passages between Huh-7 and C6/36 cells. After 10 passages, consensus mutations were identified and fitness was assayed by evaluating replication kinetics in both cell types as well as in a novel cell type (Vero) that was not utilized in any of the passage series. Viruses allowed to specialize in single host cell types exhibited fitness gains in the cell type in which they were passaged, but fitness losses in the bypassed cell type, and most alternating passages, exhibited fitness gains in both cell types. Interestingly, fitness gains were observed in the alternately passaged, cloned viruses, an observation that may be attributed to the acquisition of both host cell-specific and amphi-cell-specific adaptations or to recovery from the fitness losses due to the genetic bottleneck of biological cloning. Amino acid changes common to both passage series suggested convergent evolution to replication in cell culture via positive selection. However, intriguingly, mutations accumulated more rapidly in viruses passed in Huh-7 cells than in those passed in C6/36 cells or in alternation. These results support the hypothesis that releasing DENV from host alternation facilitates adaptation, but there is limited support for the hypothesis that such alternation necessitates a fitness trade-off. Moreover, these findings suggest that patterns of genetic evolution may differ between viruses replicating in mammalian and mosquito cells.
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“The trade-off hypothesis predicts that constraining evolution in one host species diminishes fitness in the other (Vasilakis et al., 2009).”
From Codon Pair Bias Is a Direct Consequence of Dinucleotide Bias (2016) · cites this paper as Vasilakis et al., 2009
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Citations
Cites
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Grubaugh, N. D., Gangavarapu, K., Quick, J., Matteson, N. L., de Jesus, J. G., Main, B. J., Tan, A. L., Paul, L. M., Brackney, D. E., Grewal, S., et al. (2019) · Genome biology · doi:10.1186/s13059-018-1618-7 · Cited by 979
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Self-citationC6/36 Aedes albopictus Cells Have a Dysfunctional Antiviral RNA Interference Response
Brackney, D. E., Scott, J. C., Sagawa, F., Woodward, J. E., Miller, N., Schilkey, F., Mudge, J., Wilusz, J., Olson, K. E., Blair, C. D., et al. (2010) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000856 · Cited by 327
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Self-citationArbovirus high fidelity variant loses fitness in mosquitoes and mice
Coffey, L. L., Beeharry, Y., Bordería, A. V., Blanc, H., & Vignuzzi, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111650108 · Cited by 249
Metadata
- Authors
- Vasilakis, N., Deardorff, E. R., Kenney, J. L., Rossi, S. L., Hanley, K. A., & Weaver, S. C.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- New Mexico State University (US)
- Corresponding author
- Weaver, Scott C.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-06-05
- Volume
- 5
- Issue
- 6
- Pages
- e1000467
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2685980
- OpenAlex
- W2098987669
- Cited by
- 191
- References
- 75
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 24 · 2023: 6 · 2022: 3 · 2021: 15 · 2020: 13 · 2019: 13 · 2018: 11 · 2017: 8 · 2016: 12 · 2015: 11 · 2014: 21 · 2013: 8 · 2012: 5
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH T32)
- Centers for Disease Control and Prevention (T01 CCT622892)
- U.S. Public Health Service (T01/CCT 622892)
- National Institute of Allergy and Infectious Diseases (R01AI069145, AI069145)
- National Center for Research Resources (P20RR016480)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Physical Sciences › Mathematics › Applied Mathematics › Mathematical and Theoretical Epidemiology and Ecology Models
- Keywords
- dengue virus, mosquito-borne arboviruses, host alternation, trade-off hypothesis, host adaptation, viral fitness, mutation accumulation, serial passage, C6/36 cells, Huh7 cells, Vero cells, convergent evolution, positive selection, host cell specificity
- MeSH terms
- Adaptation, Biological, Aedes, Analysis of Variance, Animals, Arboviruses, Cell Line, Chlorocebus aethiops, Dengue Virus, Humans, Kinetics, Mutation, Research Design, Selection, Genetic, Serial Passage, Vero Cells, Virulence, Virus Replication, Consensus Sequence, Sequence Analysis, RNA, Evolution, Molecular, Cell Line, Tumor
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