Recombination in Enteroviruses, a Multi-Step Modular Evolutionary Process

Abstract

RNA recombination is a major driving force in the evolution and genetic architecture shaping of enteroviruses. In particular, intertypic recombination is implicated in the emergence of most pathogenic circulating vaccine-derived polioviruses, which have caused numerous outbreaks of paralytic poliomyelitis worldwide. Recent experimental studies that relied on recombination cellular systems mimicking natural genetic exchanges between enteroviruses provided new insights into the molecular mechanisms of enterovirus recombination and enabled to define a new model of genetic plasticity for enteroviruses. Homologous intertypic recombinant enteroviruses that were observed in nature would be the final products of a multi-step process, during which precursor nonhomologous recombinant genomes are generated through an initial inter-genomic RNA recombination event and can then evolve into a diversity of fitter homologous recombinant genomes over subsequent intra-genomic rearrangements. Moreover, these experimental studies demonstrated that the enterovirus genome could be defined as a combination of genomic modules that can be preferentially exchanged through recombination, and enabled defining the boundaries of these recombination modules. These results provided the first experimental evidence supporting the theoretical model of enterovirus modular evolution previously elaborated from phylogenetic studies of circulating enterovirus strains. This review summarizes our current knowledge regarding the mechanisms of recombination in enteroviruses and presents a new evolutionary process that may apply to other RNA viruses.

Early origin and global colonisation of foot-and-mouth disease virus

“…Our analyses showed that recombination can readily occur in FMDV, especially among Euro-Asiatic serotypes and among SAT serotypes, www.nature.com/scientificreports/ but the process is likely largely constrained by epistatic interaction between regions coding for functionally related proteins, resulting in relatively clear mosaic genomic blocks of low recombination-rate regions as previously noted [17][18][19] . This phenomenon has in fact also been observed in other viruses 31,32 . Given how common it is, recombination likely plays an important role in survival and adaption of viruses in the face of new environments.…”

Dissemination of Internal Ribosomal Entry Sites (IRES) Between Viruses by Horizontal Gene Transfer

“…It can involve replicative or non-replicative mechanisms [ 2 , 3 ] and potentially serves functions that include the purging of deleterious mutations and the creation of advantageous novel genetic combinations to evade host immunity, gain resistance to antiviral agents, alter virulence and expand the host range [ 1 , 4 , 5 ]. Molecular epidemiological studies, for example, of circulating enteroviruses, have shown that recombination is a frequent occurrence in picornaviruses (e.g., [ 6 , 7 , 8 ]), and analysis of viral metagenomic data has emphasized the importance of recombination in the acquisition of novel sequences and, consequently, in the evolution of viruses [ 9 , 10 ]. In contrast to nucleotide substitution, which only allows gradual searching through evolutionary fitness space, recombination can lead to large shifts that can create beneficial genetic diversity but may also disrupt favorable combinations of co-adapted alleles [ 1 , 11 ].…”

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…Improvements in viral genomic sequencing methods have facilitated the detection of recombinants, leading to accelerated detection of these events over the past decade. Enteroviruses have been frequently observed to recombine to permit the emergence of new viral strains [127,128], and indeed OPV and circulating enteroviruses also have the capacity to generate recombinants with enhanced pathogenicity and fitness [129]. Recombination events are also frequent in human and animal AstV [130] and NoV [131].…”