Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape

Ahmed A Quadeer,Matthew R Mckay,John P Barton,Arup K Chakraborty

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.

Highlights

A goal is to identify the features of these viruses that explain their susceptibility or resistance to control by vaccination. For the latter class (e.g., human immunodeficiency virus (HIV), hepatitis C virus (HCV)), one aims to develop an understanding of the specific sets of viral protein residues that are vulnerable to mutations, and can serve as targets for vaccine-induced immune responses
As a first step in inferring the fitness landscape of vp[1], as established previously for HIV proteins[10,11,12,13,14,15], we sought to infer a probabilistic model, referred to as a prevalence landscape, that approximately describes the distribution of the sequences observed in the multiple sequence alignment (MSA)
High mutation rate is an important characteristic of viruses that can enable them to evade immune responses and propagate infection

Summary

Introduction

A goal is to identify the features of these viruses that explain their susceptibility or resistance to control by vaccination For the latter class (e.g., HIV, HCV), one aims to develop an understanding of the specific sets of viral protein residues that are vulnerable to mutations, and can serve as targets for vaccine-induced immune responses. OPV, in contrast, elicits both cellular and humoral immune responses as it is based on a live attenuated virus which replicates in the GI tract, providing better GI immunity against wild-type PV. Both vaccines have been successful in the global fight against PV

Objectives

Methods

Results

Conclusion