PARALLEL EVOLUTION OF PATHOGENIC TYPE 2 VACCINE-DERIVED POLIOVIRUSES

Under setting of low vaccine coverage, the type-2 vaccine strain may evolve over time into a neuropathogenic form. Here we propose a comprehensive model that describes the gradual increase in virus fitness from the attenuated strain into a form indistinguishable from wild-type polioviruses. Our approach relies on a novel phylogenetic model for detecting substitutions under parallel adaptive selection, and subsequent follow-up of these mutations in an experimental evolution setup of tissue culture replication. Our model detects four waves of events: (a) substitutions in the non-coding and coding regions of the virus genome, (b) recombination with other eneteroviruses, (c) synonymous substitutions presumably allowing host immune evasion, and (d) gradual reversion to wild-type. Several of these mutations have not been implicated previously and may be used for forecasting the distance between a novel cVDPV and wild-type phenotype. We show that the key features involved in the global process of regain of virulence of VDPV strains are highly predictable, underscoring the importance of adequate immunization coverage.