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Abstract
<p id="P3">Paralytic polio once afflicted almost half a million children each year.
The attenuated
oral polio vaccine (OPV) has enabled world-wide vaccination efforts, which resulted
in nearly complete control of the disease. However, poliovirus eradication is hampered
globally by epidemics of vaccine-derived polio. Here, we describe a combined theoretical
and experimental strategy that describes the molecular events leading from OPV to
virulent strains. We discover that similar evolutionary events occur in most epidemics.
The mutations and the evolutionary trajectories driving these epidemics are replicated
using a simple cell-based experimental setup where the rate of evolution is intentionally
accelerated. Furthermore, mutations accumulating during epidemics increase the replication
fitness of the virus in cell culture and increase virulence in an animal model. Our
study uncovers the evolutionary strategies by which vaccine strains become pathogenic,
and provides a powerful framework for rational design of safer vaccine strains and
for forecasting virulence of viruses.
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