Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape
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s41467-019-14174-2.pdf
Description
Published version
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2.94 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Quadeer, Ahmed A
Barton, John P
Chakraborty, Arup K
McKay, Matthew R
Date Issued
2020
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2020, The Author(s). Vaccination has essentially eradicated poliovirus. Yet, its mutation rate is higher than that of viruses like HIV, for which no effective vaccine exists. To investigate this, we infer a fitness model for the poliovirus viral protein 1 (vp1), which successfully predicts in vitro fitness measurements. This is achieved by first developing a probabilistic model for the prevalence of vp1 sequences that enables us to isolate and remove data that are subject to strong vaccine-derived biases. The intrinsic fitness constraints derived for vp1, a capsid protein subject to antibody responses, are compared with those of analogous HIV proteins. We find that vp1 evolution is subject to tighter constraints, limiting its ability to evade vaccine-induced immune responses. Our analysis also indicates that circulating poliovirus strains in unimmunized populations serve as a reservoir that can seed outbreaks in spatio-temporally localized sub-optimally immunized populations.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemistry
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1038/S41467-019-14174-2
https://doi.org/10.1038/S41467-019-14174-2
