Serial Recombination during Circulation of Type 1 Wild-Vaccine Recombinant Polioviruses in China

Abstract

Type 1 wild-vaccine recombinant polioviruses sharing a 367-nucleotide (nt) block of Sabin 1-derived sequence spanning the VP1 and 2A genes circulated widely in China from 1991 to 1993. We surveyed the sequence relationships among 34 wild-vaccine recombinants by comparing six genomic intervals: the conserved 5-untranslated region (5-UTR) (nt 186 to 639), the hypervariable portion of the 5-UTR (nt 640 to 742), the VP4 and partial VP2 genes (nt 743 to 1176), the VP1 gene (nt 2480 to 3385), the 2A gene (nt 3386 to 3832), and the partial 3D gene (nt 6011 to 6544). The 5-UTR, capsid (VP4-VP2 and VP1), and 2A sequence intervals had similar phylogenies. By contrast, the partial 3D sequences could be distributed into five divergent genetic classes. Most (25 of 34) of the wild-vaccine recombinant isolates showed no evidence of additional recombination beyond the initial wild-Sabin recombination event. Eight isolates from 1992 to 1993, however, appear to be derived from three independent additional recombination events, and one 1993 isolate was derived from two consecutive events. Complete genomic sequences of a representative isolate for each 3D sequence class demonstrated that these exchanges had occurred in the 2B, 2C, and 3D genes. The 3D gene sequences were not closely related to those of the Sabin strains or 53 diverse contemporary wild poliovirus isolates from China, but all were related to the 3D genes of species C enteroviruses. The appearance within approximately 2.5 years of five recombinant classes derived from a single ancestral infection illustrates the rapid emergence of new recombinants among circulating wild polioviruses.

Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages

“…Serotypes 1, 2 and 3 of wild-type PVs have been reported to recombine with each other (Dahourou et al, 2002;Furione et al, 1993). Wild-type and OPV strains have been reported to recombine (Dahourou et al, 2002;Georgescu et al, 1995;Guillot et al, 2000;Liu et al, 2000Liu et al, , 2003Yang et al, 2003) and PVs have been shown to recombine with serotypes of HEV-C (Brown et al, 2003;Jiang et al, 2007;Rousset et al, 2003). Furthermore, vaccine-derived PV strains, defined as having more than 1 % nucleotide differences in the VP1 protein coding region (reviewed recently by Agol, 2006;Kew et al, 2004), have been reported to have an interserotypic recombinant genome (Blomqvist et al, , 2004Martin et al, 2002) as well as a recombinant genome with a non-structural region from an unknown HEV-C strain (Arita et al, 2005;Kew et al, 2002Kew et al, , 2004Rakoto-Andrianarivelo et al, 2008;Rousset et al, 2003;Shimizu et al, 2004).…”

Molecular Analysis of Enteroviruses

“…In EV-C species, natural interserotypic recombination within the capsid region of PVs appears to be rare, probably because structural incompatibilities restrict the fitness of most interserotypic recombinants [142]. In contrast, interserotypic recombinants excreted by recent vaccinees exposed to tOPV and recombinants among circulating wild-type PVs and vaccinederived PVs usually have crossovers restricted to the noncapsid region [142].…”

“…In contrast, interserotypic recombinants excreted by recent vaccinees exposed to tOPV and recombinants among circulating wild-type PVs and vaccinederived PVs usually have crossovers restricted to the noncapsid region [142]. PVs recombine actively with each other and with other closely related EV-C members, a process which might offset the effects of accumulation of deleterious mutations arising in some lineages [46,121,142,143].…”

“…In addition, the prototype EV-C strains are recombinant relative to each other [92], and circulating EVs commonly recombine with wild-type and vaccine PVs [144]. Studies have shown that, compared with VP1, the 5' UTR of CV-A (sero)types and PVs has frequently been subject to recombination [17,145], indicating that interserotypic recombination may play a major role in the evolution of some of these viruses.…”

Εμβολιακά Στελέχη Πολιοϊών - Συσχέτιση Ανασυνδυασμών Με Δευτεροταγείς RNA Δομές

“…Επιπλέον, ο περιορισμός των λειτουργικών διαμορφώσεων των πρωτεϊνικών μορίων σε περιοχές κρίσιμες για τη σταθερότητα του καψιδίου, Kew et al, 2002;Rousset et al, 2003;Liu et al, 2003;Shimizu et al, 2004;Liang et al, 2006). Επίσης, ο ανασυνδυασμός μπορεί να συνετέλεσε στην αύξηση της αρμοστικότητας του στελέχους 7/b/97, μέσω αντικατάστασης των καθοριστών θερμοευαισθησίας, οι οποίοι εδράζονται στις 3D και 3UTR περιοχές.…”