Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape

Nat Commun. 2020 Jan 17;11(1):377. doi: 10.1038/s41467-019-14174-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / genetics
  • Capsid Proteins / classification
  • Capsid Proteins / genetics*
  • Computational Biology
  • Disease Outbreaks
  • Evolution, Molecular
  • Genetic Fitness*
  • HIV / genetics
  • Humans
  • Models, Genetic
  • Mutation Rate*
  • Mutation*
  • Phylogeny
  • Poliomyelitis / epidemiology*
  • Poliomyelitis / immunology
  • Poliomyelitis / virology*
  • Poliovirus / genetics*
  • Poliovirus / immunology
  • Prevalence
  • Probability
  • Viral Proteins / classification
  • Viral Proteins / genetics
  • Viral Vaccines

Substances

  • Antigens, Viral
  • Capsid Proteins
  • VP1 protein, Poliovirus
  • Viral Proteins
  • Viral Vaccines