Frequent isolation of intertypic poliovirus recombinants with serotype 2 specificity from vaccine‐associated polio cases

Abstract

Five representatives from a collection of 21 Sabin type 2-like poliovirus strains isolated from paralytic poliomyelitis cases in two regions of the USSR have been subjected to limited nucleotide sequencing. All proved to be intertypic recombinants having the genes encoding capsid proteins of Sabin 2 origin and a 3'-end portion of the genome derived from either type 1 (3 isolates) or type 3 (2 isolates) Sabin strains. The crossover points in all the 5 genomes have been mapped to different loci of the P3 region. At least 6 additional isolates from the same collection (and 2 isolates from healthy contacts), appeared to have a type 2/type 1 recombinant genome, as judged by oligonucleotide mapping. The biological significance of frequent occurrence of recombinants among field isolates of vaccine-related strains is discussed.

Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

“…Given the high frequency of recombinant genomes in the OPV strains excreted by healthy vaccinees (22; N. Cuervo et al, unpublished results), their contacts in the community, and patients with VAPP (9,11,21; this study), it seems highly likely that genetic recombination is involved in the natural evolution of Sabin strains. OPV strains are reputed to grow less efficiently in the human gut than wild epidemic PVs.…”

“…Natural genetic recombination in PV, another mechanism of variation in Sabin strains, was demonstrated many years ago (14,32,33) (for reviews, see references 4 and 19). 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vaccine/ wild (V/W) PV recombinants have been found, in which vaccine-specific segments of the Sabin virus genome have been replaced by nonvaccine sequences derived from wild PVs or, perhaps, from non-polio enteroviruses (NPEVs) (10,19,21,30).…”

Geographical genotypes (geotypes) of poliovirus case isolates from the former Soviet Union: relatedness to other known poliovirus genotypes

“…For PCR amplification, either total RNA extracted from infected cells, or RNA present in tissue culture fluid after complete CPE of the infected cells were used (Yang et aL,i991). RNAs used for sequence analysis were extracted from purified virions (Lipskaya et al, 1991).…”

“…Thus, some 130 000 cases of paralytic poliomyelitis were estimated to occur over the world in 1991 (World Health Organization, 1991). Although a tiny proportion of them could be linked to the use of the live Sabin poliovaccine (Assaad et al, 1982;Nkowane et al, 1987;Lipskaya et al, 1991) naturally circulating 'wild-type' poliovirus strains are the principal aetiological agents of the disease.…”

A Sabin vaccine-derived field isolate of poliovirus type 1 displaying aberrant phenotypic and genetic features, including a deletion in antigenic site 1.

“…Another well-known characteristic of poliovirus that contributes to genetic variability is its ability to recombine with other serotypes (intertypic recombinants : Cammack et al, 1988 ;Johnson & Semler, 1988 ;King, 1988 ;Lipskaya et al, 1991 ;Furione et al, 1993) or with another genome of the same serotype (intratypic recombinants : Zheng et al, 1993 ;Georgescu et al, 1994 ;Friedrich et al, 1996). During replication in humans, and upon transmission between hosts, some of the mutations generated are enriched.…”