Modular Evolution and Emergence of Enteroviruses Through Genetic Recombination

Abstract from Fourth National Congress of Virology with International Participation /Days of Virology in Bulgaria Sofia, May 18th - 20th, 2016

Francis Delpeyroux

Unit Biology of Enteric Viruses, INSERM U994,

WHO-CC on Enteroviruses, Institut Pasteur,

Recombination shapes viral genomes, including those of the pathogenic circulating vaccine-derived polioviruses (cVDPVs), responsible for poliomyelitis outbreaks. The genomes of cVDPVs consist of sequences from vaccine poliovirus (PV) and other enteroviruses (EVs). We investigated the plasticity of PV genomes and the effects of recombination in the 5’ untranslated region (5’ UTR) and 3’ half of the genome.

We rescued 3’ and 5’ UTR-defective PV genomes by cotransfecting cells with genomic RNAs from human EV species EV-A to -D. Hundreds of recombinants were isolated, revealing a striking genetic plasticity, with homologous and nonhomologous recombination sites mostly clustered in hotspots. Intertypic recombination either affected replication and virulence or was neutral and in certain cases improved viral fitness. This study illustrates how RNA viruses can acquire mosaic genomes through modular intra- or inter-species recombination, favoring the emergence of new recombinant strains.