Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

Abstract

In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3 moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.

Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region.

“…And fourth, since the rDEN4⌬30 vector is common to all the chimeric viruses of the tetravalent formulation, recombination between the vaccine serotypes would not lead to loss of the attenuating mutation or reversion to a wt phenotype. Recombination between components of the trivalent polio vaccine has been observed, 42 and naturally occurring recombinant dengue viruses have been described. 43 In summary, the DEN-4 vaccine candidate virus 2A⌬30 was well tolerated and induced an acceptable neutralizing antibody response in each of the 20 volunteers in this initial Phase I clinical trial.…”

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).…”

Full-length open reading frame of a recombinant hepatitis C virus strain from St Petersburg: proposed mechanism for its formation

“…A high mutation rate is considered to be a major factor behind its genetic diversity (Simmonds, 1999(Simmonds, , 2001Farci & Purcell, 2000). Recombination provides another mechanism for creating genetic variation and is known to be widespread among nonsegmented RNA viruses, including other members of Flaviviridae (Lai, 1992;Figlerowicz et al, 1997;Worobey et al, 1999;Guillot et al, 2000;Twiddy & Holmes, 2003). Some viruses, such as coronaviruses, bromoviruses and carmoviruses, for example turnip crinkle virus (TCV), may undergo both homologous and non-homologous recombination, while some non-segmented plus-strand RNA viruses, such as picornaviruses, may only undergo homologous recombination (Lai, 1992).…”