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Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.

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.

SUBMITTER: Quadeer AA

PROVIDER: S-EPMC6969152 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.

Quadeer Ahmed A AA Barton John P JP Chakraborty Arup K AK McKay Matthew R MR

Nature communications 20200117 1

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 intrin ...[more]

PMID: 31953427

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Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.

Publications

Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.

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