Antigenic Structure of Polioviruses of Serotypes 1, 2 and 3

Abstract

SUMMARYThe antigenic sites recognized by monoclonal antibodies with neutralizing activity for the Sabin vaccine strains of poliovirus of serotypes 1, 2 and 3 have been studied by the isolation and characterization of mutants resistant to neutralization by antibody. Three distinct sites have been identified which are designated site 1, site 2 and site 3. Site 1 includes a region of 12 amino acids of VP1, from residues 89 to 100, and a corresponding region of VP1 has been identified as an antigenic site for poliovirus 2. This site was strongly immunodominant in type 2 and type 3 but was not detected for poliovirus 1. Site 2 is a complex site including residues 220 to 222 from VP1 (site 2a) with residues including 169 and 170 and others of VP2 (site 2b). Both site 2a and site 2b have been detected in type 1 poliovirus, while as yet only site 2b has been detected in type 3 poliovirus. Site 3 is a complex site including residues 286 to 290 from VP1 (site 3a) with residues including 58 and 59 and others of VP3 (site 3b). Both sites 3a and 3b have been detected in type 3 poliovirus, while as yet only site 3b has been detected in type 1 poliovirus. INTRODUCTIONPoliovirus is a picornavirus of the enterovirus genus occurring in three distinct serotypes. The virion consists of a single strand of messenger-sense RNA enclosed in a capsid made up of 60 copies of each of the four structural proteins VP1, VP2, VP3 and VP4. Nucleotide sequences of the genomic RNA of several strains of poliovirus have been published (Kitamura et al., 1981 ;Toyoda et al., 1984;Cann et al., 1984) and the X-ray crystallographic structure of the Mahoney strain of type 1 poliovirus has been solved to 2.9 A (0-29 nm) resolution .

Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2, 3 and 4

“…The constructs made are shown in Table 1. Viruses were recovered by transfection of Hep2c cells (Burke et al, 1988) and the sequence of the insert was checked by sequencing the genomic RNA (Minor et al, 1986). All viruses were neutralized by pooled human serum and infection was prevented by an MAb specific for the poliovirus receptor (Minor et al,199O).…”

“…The antigenic structure of poliovirus has been studied extensively, and several sites to which neutralizing antibodies bind have been identified by the isolation and characterization of antigenic variants (Minor et al, 1983(Minor et al, , 1986Diamond et al, 1985;Blondel et al, 1986;Page et al, 1988;Wiegers et al, 1989). The atomic structures of the type 1 strain Mahoney (Hogle et al, 1985) and the Sabin type 3 strain Leon 12alb (Filman et al, 1989) have been determined, and the antigenic sites have been shown to form apparently distinct structural features on the virus surface.…”

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

“…PV2-32191 had two substitutions in the capsid coding region. The first was in VP3, at the recognized neutralizing antigenic site 3B (Minor et al, 1986a), and the second in VP1-143, in the known attenuation site exposed in the DE-loop (Hogle et al, 1985). The amino acid substitution in PV2-32189+AP1, in addition to the VP1-143 substitution, resided in the nonstructural protein coding region in 2A, with no known specific biological function.…”

Structure, function and evolution of picornaviruses

“…Direct analysis using monoclonal antibody escape mutants showed that some of these regions corresponded to neutralizing antigenic sites and this has allowed the production of synthetic peptides as potential vaccines and for probing the antigenic structure (Minor et al, , 1986aFerguson et al, 1985;DiMarchi et al, 1986;Sherry et al, 1986). Alignment of sequences also enables the corresponding antigenic regions in viruses not studied directly to be identified.…”