Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis

Abstract

The isolation of a capsid intertypic poliovirus recombinant from a child with vaccine-associated paralytic poliomyelitis is described. Virus 31043 had a Sabin-derived type 3-type 2-type 1 recombinant genome with a 5-end crossover point within the capsid coding region. The result was a poliovirus chimera containing the entire coding sequence for antigenic site 3a derived from the Sabin type 2 strain. The recombinant virus showed altered antigenic properties but did not acquire type 2 antigenic characteristics. The significance of the presence in nature of such poliovirus chimeras and the consequences for the current efforts to detect potentially dangerous vaccine-derived poliovirus strains are discussed in the context of the global polio eradication initiative.Poliovirus, the agent responsible for paralytic poliomyelitis, is a human enterovirus member of the family Picornaviridae, a group of nonenveloped positive-strand RNA viruses. The coding region of the genome is preceded by a long 5Ј noncoding region (NCR) of approximately 740 nucleotides that contains important determinants of virulence. The 3Ј end of the genome consists of a short NCR of about 70 nucleotides that is also implicated in RNA replication (33). The coding region is translated as a single polyprotein and is then processed to generate the viral capsid (VP1 to VP4) and the nonstructural proteins. The antigenic determinants for poliovirus-neutralizing antibodies are located on surface-exposed loops in the capsid proteins VP1, VP2, and VP3. Four main antigenic sites have been identified by the use of murine monoclonal antibodies (MAbs) (30).Genomic RNA recombination is a common event during poliovirus evolution. The oral poliovaccine (OPV) consists of live attenuated strains of the three polio serotypes, which replicate in the guts of immunocompetent vaccinees for periods that range between several weeks and 3 months. A high proportion of type 2 and type 3 polio isolates excreted by healthy vaccinees and patients with vaccine-associated paralytic poliomyelitis (VAPP), have been found to be intertypic recombi-

Evidence of intratypic recombination in natural populations of hepatitis C virus

“…Our phylogenetic analyses based on two different genomic regions, 59UTR-core and NS5B, demonstrate the existence of natural intragenotypic HCV recombinant strains (1a/1b) circulating in the Peruvian population. The recombination breakpoint for non-segmented positive-strand RNA viruses, such as polioviruses and other picornaviruses (Santti et al, 1999;Guillot et al, 2000;Kew et al, 2002), as well as members of the family Flaviviridae, are often located in the part of the genome encoding the non-structural proteins but sometimes in genes encoding structural proteins (CostaMattioli et al, 2003;Martin et al, 2002). Moreover, several possible recombination breakpoints have been identified in other RNA viruses, such as human immunodeficiency virus (HIV), and many more are being reported (Onafuwa et al, 2003;Vidal et al, 2003;Strimmer et al, 2003;Najera et al, 2002).…”

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

“…The enterovirus recombination sites are located in the 59 non-coding region (NCR) and in the non-structural part of the 7500 nt genome in genes coding for proteins 2A, 2B, 2C and 3D. In addition, recombination in the capsid protein VP1 coding region has been shown Dedepsidis et al, 2008;Liu et al, 2000;Martin et al, 2002), as well as recombination in the VP2 protein coding gene (Kyriakopoulou et al, 2006). In addition to within-species recombination events, interspecies recombination has been suggested for HEV-B and HEV-C strains (Bolanaki et al, 2007).…”

“…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). The enterovirus recombination sites are located in the 59 non-coding region (NCR) and in the non-structural part of the 7500 nt genome in genes coding for proteins 2A, 2B, 2C and 3D.…”

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

“…According to this limited set of HRV sequences, it has been suggested that the main force driving the genetic diversification of HRV may be genetic drift rather than intra-or interserotypic recombination, which, in contrast, are common in closely related HEV genomes (Brown et al, 2003; Lindberg et al, 2003;Norder et al, 2002;Santti et al, 1999). In HEV, the recombination sites are usually located in genomic regions encoding non-structural proteins, but have also occasionally been found in the VP1 capsid protein coding region Martin et al, 2002).HRV are classified into two groups according to receptors used in cellular attachment and entry. Twelve HRV-A serotypes (HRV1A, 1B, 2, 23, 25, 29, 30, 31, 44, 47, 49 and 62), the minor receptor group, use members of the lowdensity lipoprotein receptor (LDLR) family, which are proposed to bind their ligands by electrostatic interactions with negatively charged ligand-binding domains (Gruenberger et al, 1995;Hofer et al, 1994;Marlovits et al, 1998;Vlasak et al, 2005b).…”