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Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape

Author

Listed:
  • Ahmed A. Quadeer

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • John P. Barton

    (University of California)

  • Arup K. Chakraborty

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    MIT and Harvard)

  • Matthew R. McKay

    (The Hong Kong University of Science and Technology, Clear Water Bay
    The Hong Kong University of Science and Technology, Clear Water Bay)

Abstract

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.

Suggested Citation

  • Ahmed A. Quadeer & John P. Barton & Arup K. Chakraborty & Matthew R. McKay, 2020. "Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14174-2
    DOI: 10.1038/s41467-019-14174-2
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    Cited by:

    1. Hang Zhang & Ahmed Abdul Quadeer & Matthew R. McKay, 2023. "Direct-acting antiviral resistance of Hepatitis C virus is promoted by epistasis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Avik Biswas & Allan Haldane & Ronald M Levy, 2022. "Limits to detecting epistasis in the fitness landscape of HIV," PLOS ONE, Public Library of Science, vol. 17(1), pages 1-22, January.

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