Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications

Abstract

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These “weak” segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination.

Picornavirus RNA Recombination Counteracts Error Catastrophe

“…Based on these structural insights, we suspect that Leu420 helps to distinguish between homologous and nonhomologous partners in recombination by playing an indirect role in favoring proper Watson-Crick base pairing between template and product strands at the active site. The degree of homology between viral RNA products and partners in recombination ranges from 3 to 30 nucleotides (28). When Leu420 reinforces interactions between homologous partners, three nucleotides from the active site, the polymerase can more efficiently resume elongation and produce recombinant genomes.…”

Emergency Services of Viral RNAs: Repair and Remodeling

“…Indeed, recombination between OPV serotypes is quite common (310,(348)(349)(350)(351)(352). The pattern of distribution of the crossovers in a large set of such intertypic vaccines/vaccine recombinants allowed us to propose the existence of serotype-specific "weak" (fitness-decreasing) regions which are strongly selected against (353). Intriguingly, the locations of these regions may not necessarily correlate with the locations of the known attenuating mutations, raising questions about the nature of their apparent weakness.…”

An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms

“…Intraspecies recombination is well documented for enterovirus species A (39, 67), species B (38, 68), species C (36) and species D viruses (69, 70), as well as rhinovirus species groups (37, 71), parechoviruses (35) and non-human enteroviruses (41). cVDPVs arise, in part, due to improved fitness from genetic exchange with non-polio group C enteroviruses in the field (46–50). Now that we appreciate the molecular and ecological conditions that contribute to genetic exchange between picornaviruses, we may be able to exploit recombination to combat human disease.…”

“…When two related viruses co-infect a cell, sexual RNA replication mechanisms lead to the generation of chimeric RNA genomes, which are often fit, culminating in sustained host-to-host transmission. Circulating vaccine-derived polioviruses, obstacles to poliovirus eradication, are products of sexual RNA replication mechanisms – formed when unfit portions of OPV RNA genomes recombine with more fit regions of non-polio group C enteroviruses (46–48). When recombinant progeny are fit, as occurs in the case of circulating vaccine-derived polioviruses, the recombinant strains circulate from host-to-host (49, 50).…”