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bioRxiv · 10.1101/273060

Genetic recombination of poliovirus facilitates subversion of host barriers to infection

Acevedo, A.·Woodman, A.·Arnold, J. J.·Yeh, M. T.·Evans, D.·Cameron, C. E.·Andino, R.
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Abstract

The contribution of RNA recombination to viral fitness and pathogenesis is poorly defined. Here, we isolate a recombination-deficient, poliovirus variant and find that, while recombination is detrimental to virus replication in tissue culture, recombination is important for pathogenesis in infected animals. Notably, recombination-defective virus exhibits severe attenuation following intravenous inoculation that is associated with a significant reduction in population size during intra-host spread. Because the impact of high mutational loads manifests most strongly at small population sizes, our data suggest that the repair of mutagenized genomes is an essential function of recombination and that this function may drive the long-term maintenance of recombination in viral species despite its associated fitness costs.\n\nSignificance StatementRNA recombination is a widespread but poorly understood feature of RNA virus replication. For poliovirus, recombination is involved in the emergence of neurovirulent circulating vaccine-derived poliovirus, which has hampered global poliovirus eradication efforts. This emergence illustrates the power of recombination to drive major adaptive change; however, it remains unclear if these adaptive events represent the primary role of recombination in virus survival. Here, we identify a viral mutant with a reduced rate of recombination and find that recombination also plays a central role in the spread of virus within animal hosts. These results highlight a novel approach for improving the safety of live attenuated vaccines and further our understanding of the role of recombination in virus pathogenesis and evolution.

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Acevedo, A., Woodman, A., Arnold, J. J., Yeh, M. T., Evans, D., Cameron, C. E., Andino, R.. 2018-02-28. Genetic recombination of poliovirus facilitates subversion of host barriers to infection. https://doi.org/10.1101/273060

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