Tripartite genome organization of a natural type 2 vaccine/nonvaccine recombinant poliovirus

Abstract

Intertypic vaccine/vaccine recombinant polioviruses are frequently isolated from vaccine-associated paralytic poliomyelitis cases (VAPP). We identified a vaccine/ nonvaccine poliovirus recombinant as the causative agent of a lethal VAPP. Partial RNA sequencing revealed a tripartite recombinant structure of the viral genome. This consisted of a central capsid core of vaccine origin flanked by two units of nonvaccine origin. The first nonvaccine genomic unit spanned the whole 5' noncoding region, and the second one almost the entire nonstructural protein-coding region and the 3' noncoding region. Amino acid and nucleotide sequence similarities in the 3' and 5' unidentified regions indicated that the viral donor(s) were poliovirus species, suggesting recombination between a vaccine-derived and a wild poliovirus. The nonvaceine donor(s) could not be identified among the investigated wild polioviruses cocirculating in the same geographical area. This is the first report of a natural recombination event occurring in the 5' genomic extremity of poliovirus. The neurovirulence for transgenic mice and the pathogenicity for humans of the recombinant suggested that the modular genomic organization of this virus might have conferred a selective advantage over its vaccine parent.

Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

“…Strain P2-V/598/80 has been shown to be a type 2 V/W recombinant in which the only conserved vaccine-derived sequence is the capsid-coding region studied (10). Almost all of the 5ЈUTR, the nonstructural protein-coding region, and the 3ЈUTR have been replaced by wild sequences.…”

“…These segments were thought to be derived from modified Sabin strains, wild PV, or from NPEVs. One of these recombinants was found to be a double recombinant containing wild sequences throughout the genome except in the capsid-encoding region (10). In this study, we further analyzed the genetic characteristics of these modified OPV-derived strains and assessed the occurrence of such strains in cases of VAPP.…”

“…Sabin vaccine PV-derived strains with recombinant intertypic genomes have been found to occur naturally (17,22) and to be selected frequently in the gut of VAPP patients (9,11,21). In some cases, vaccine/ wild (V/W) PV recombinants have been found, in which vaccine-specific segments of the Sabin virus genome have been replaced by nonvaccine sequences derived from wild PVs or, perhaps, from non-polio enteroviruses (NPEVs) (10,19,21,30).…”

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).…”

Μοριακή ταυτοποίηση και διερεύνηση της εξέλιξης των echo ιών

“…Έχει υποστηριχθεί, ότι στην πλειοψηφία των μελετημένων περιπτώσεων πολιοϊών, ο ανασυνδυασμός υφίσταται στο μη -δομικό γονιδίωμα και συνήθως στο τμήμα 2Α -2C. Σε κάποιες περιπτώσεις έχουν αναφερθεί γεγονότα ανασυνδυασμού μεταξύ της 5΄ NTR και της P1 κωδικής περιοχής (του καψιδίου) (Georgescu et al, 1995), ενώ ο ανασυνδυασμός εντός του γενωμικού τμήματος, που κωδικοποιεί για τις πρωτεΐνες του καψιδίου, φαίνεται να αποτελεί περισσότερο εξαίρεση παρά κανόνα των περιπτώσεων ανασυνδυασμού (Blomquist et al, 2003).…”