Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape

• Published in: Nature communications Vol. 11; no. 1; pp. 377 - 13
• Main Authors: Quadeer, Ahmed A., Barton, John P., Chakraborty, Arup K., McKay, Matthew R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.01.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/250; 631/326/596/2554; Antibodies; Antigens, Viral - genetics; Capsid protein; Capsid Proteins - classification; Capsid Proteins - genetics; Computational Biology; Disease Outbreaks; Evolution, Molecular; Fitness; Genetic Fitness; HIV; HIV - genetics; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immune response; Immunization; Models, Genetic; multidisciplinary; Mutation; Mutation Rate; Mutation rates; Outbreaks; Phylogeny; Poliomyelitis - epidemiology; Poliomyelitis - immunology; Poliomyelitis - virology; Poliovirus - genetics; Poliovirus - immunology; Populations; Prevalence; Probabilistic models; Probability; Proteins; Reproductive fitness; Science; Science (multidisciplinary); Vaccination; Vaccines; Viral Proteins - classification; Viral Proteins - genetics; Viral Vaccines; VP1 protein
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-14174-2

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. Poliovirus has a higher mutation rate than HIV, yet has been almost eradicated by vaccination while an effective vaccine against HIV does not exist. Here, the authors develop a fitness model for poliovirus viral protein 1 to show that it is subject to stringent evolutionary constraints that limit its ability to avoid vaccine-induced immune responses.