Recombination between Poliovirus and Coxsackie A Viruses of Species C: A Model of Viral Genetic Plasticity and Emergence

Abstract

Genetic recombination in RNA viruses was discovered many years ago for poliovirus (PV), an enterovirus of the Picornaviridae family, and studied using PV or other picornaviruses as models. Recently, recombination was shown to be a general phenomenon between different types of enteroviruses of the same species. In particular, the interest for this mechanism of genetic plasticity was renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs), which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs had mosaic genomes constituted of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C), in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different HEV-C types. This viral ecosystem showed a surprising and extensive biodiversity associated to several types and recombinant genotypes, indicating that intertypic genetic recombination was not only a mechanism of evolution for HEV-C, but an usual mode of genetic plasticity shaping viral diversity. Results suggested that recombination may be, in conjunction with mutations, implicated in the phenotypic diversity of enterovirus strains and in the emergence of new pathogenic strains. Nevertheless, little is known about the rules and mechanisms which govern genetic exchanges between HEV-C types, as well as about the importance of intertypic recombination in generating phenotypic variation. This review summarizes our current knowledge of the mechanisms of evolution of PV, in particular recombination events leading to the emergence of recombinant cVDPVs.

Disease Trends and Characteristics of Circulating Vaccine derived Poliovirus Isolated in the National Reference Polio Laboratory from the Democratic Republic of Congo

“…One of the main goals of the WHO Global Polio Eradication Initiative (GPEI) has been the live, attenuated OPV [17,18]. Once WPV transmission has been stopped globally like in the DRC, the vaccine-viruses will be the only source of live polioviruses in the community and could potentially lead to the re-emergence of polio.…”

Éradication de la poliomyélite et émergence de poliovirus pathogènes dérivés du vaccin

“…Il faut aussi remarquer que les déterminants majeurs de l'atténuation des souches vaccinales Sabin, qui se trouvent dans la région 5' non codante et affectent l'efficacité de la traduction, ont subi, chez les cPVDV, des réversions vers le géno-type sauvage [13,15,20]. Par ailleurs, de nombreux cPVDV ont acquis une région 5' non codante provenant d'HEV-C non-PV, ce qui suggère que la recombinaison peut contribuer de manière indirecte à la réversion des déterminants d'atténuation situés dans cette région.…”

“…Il faut aussi souligner l'importance de la recherche fondamentale visant à comprendre les mécanismes d'émergence de ces virus. Là encore, les études menées à Madagascar, au Cameroun, et dans les autres pays du REIP, en étroite collaboration avec l'Institut Pasteur de Paris, ont montré la parenté entre certaines séquences du génome des cPVDV et celles de souches locales de CVA de la même espèce, en particulier les CVA-17 et CVA-13, suggérant fortement un rôle de la recombinaison entre PV et CVA de la même espèce, dans l'émergence des cPVDV [4,20]. Ces travaux de recherche, ainsi que ceux d'autres collègues à l'étranger, ont déjà des conséquences pour l'amélioration des stratégies de vaccination et de surveillance.…”

The Impact of a Panenterovirus Vp1 Assay on Our Perception of the Enterovirus Diversity Landscape of a Sample

“…Recombination is one of the mechanisms used by enteroviruses for evolution and often result in the emergence of new clades with variant phenotype(s), sometimes including increased transmissibility and pathogenicity [5]. Enterovirus coinfection is however, a prerequisite for recombination between different enterovirus genomes.…”

“…The enterovirus genome has been described as 'a mosaic' [5] because of the frequency of recombination and the observation that a single genome could undergo multiple recombination events. Recombination is one of the mechanisms used by enteroviruses for evolution and often result in the emergence of new clades with variant phenotype(s), sometimes including increased transmissibility and pathogenicity [5].…”