Antigenic Variation among 173 Strains of Type 3 Poliovirus Isolated in Finland during the 1984 to 1985 Outbreak

Abstract

SUMMARY Antigenic properties of 128 clinical type 3 poliovirus isolates of the 1984 to 1985Finland outbreak from 95 persons and 45 strains from sewage water specimens were evaluated using five neutralizing monoclonal antibodies (MAbs) directed against an antigenic site (designated site 1) on VP1 at amino acids 89 to 100. All five MAbs neutralized the type 3 poliovirus strains used in the vaccines, P3/Saukett and P3/Sabin, but none of them neutralized the prototype strain of the outbreak (P3/Finland/ 23127/84). Forty-six percent of the clinical isolates resembled the prototype strain (class A) while the rest of the isolates were neutralized by one or more of the MAbs (classes B to D). Although an antigenic drift from A to one of the other classes was observed in sequential specimens from several individuals, no clear-cut overall change in the class distribution was found within the 3 months time span of the outbreak. Homogeneous virus populations were isolated from the sewage specimens using a microtitre endpoint dilution method. The last positive sewage specimens which were obtained in January to February 1985 still had a majority of the class A strain. Some of the clinical isolates were also tested using MAbs directed against distinct antigenic sites. These studies showed that strains that gave the same pattern of reactivity with site 1 MAbs could be differentiated using antibodies directed against other sites. Fifteen strains belonging to different antigenic subclasses were subjected to partial RNA sequencing of the genome region coding for antigenic site t. The antigenic variation was usually, but not always associated with corresponding amino acid substitutions in antigenic site 1. These results indicate that the antigenic sites of type 3 poliovirus vary extensively within a given outbreak and even during replication in a given host. This variation may have both pathogenetic and epidemiological significance. INTRODUCTIONThere are three distinct serotypes of poliovirus that can be distinguished from each other in neutralization tests using polyclonal antisera. Individual clinical poliovirus isolates can be easily classified into one of the three serotypes using unabsorbed antisera. The poliovirus strains used in vaccines were isolated several decades ago but still appear to induce antibodies that protect well against the poliovirus strains that are prevalent today. This would suggest that the antigenic structure of polioviruses is relatively stable. In contrast, it has been shown by oligonucleotide fingerprinting (Nottay et al., 1981 ;Minor et al., 1982) that the genome of polioviruses (like that of other RNA viruses) can vary remarkably during replication in vivo.At least three separate antigenic sites are known to be involved in neutralization of polioviruses. Regions of the three major structural proteins (VP1, 2 and 3) have been identified as antigenic sites and designated sites 1, 2 and 3 (Minor et al., 1985). These sites have also been

Generation of virus genetic lineages during an outbreak of poliomyelitis

“…If strains were available from several specimens of a person we chose a strain from the first specimen to be included in this collection. The eight healthy excretor strains were isolated as homogeneous populations directly from faecal extracts using the endpoint dilution method in microwell cultures of Vero cells (Huovilainen et al, 1988), and the standard method by inoculation into tubes of continuous monkey kidney cell lines (Vero, GMK, LLC-MK2) or primary human amnion cells was used in the isolation of the rest of the strains. The latter isolates were used for RNA extraction at the third passage level.…”

“…The viral RNA was sequenced by the dideoxynucleotide chain termination method, as described (Huovilainen et al, 1988). The six oligonucleotide primers for the 5' NCR, synthesized using the solid phase phosphoramidite method on an Applied Biosystems 381A DNA synthesizer, were targeted to the follow- Nucleotide positions are numbered according to Hughes et aL (1986).…”

“…Recombination is known to occur in members of the Picornaviridae family and this increases the genetic diversity. Accordingly, genetic variation has been demonstrated among polioviruses during epidemics (Nottay et al, 1981 ;Huovilainen et al, 1988) and even during the excretion period in one individual Huovilainen et al, 1987;Kinnunen et al, 1990). …”

Evolution of influenza B/Victoria/2/87-like viruses: occurrence of a genetically conserved virus under conditions of low epidemic activity

“…The viral RNA was sequenced by the dideoxynucleotide chain termination method, as described by Huovilainen et al (1988). The oligonucleotide primers used were: 36-GAAGGCAATAATTGTACT-53, 201-TGCAAATCTCAAAGG-215, 370-ATGCACGA-CAGAACA-384, 488-TTGGAACCTCAGGATCTT-GC-507, 628-GGAGAAGACCAAATTACT-645, 844-GGAAAAACAGGAACA-858 and 973-AAA-TACGGTGGATTAAA-989 (nucleotide positions are numbered according to Rota et al, 1990).…”

Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

“…The more pronounced differences in the AgS2a of PV1-RC2010 compared with the WPV1s from the Tajikistan outbreak may have facilitated a higher fraction of poliomyelitis in preimmunized individuals in the ROC outbreak. Antigenic drift in PV has been suggested sporadically (36)(37)(38)(39), but the epidemiologic and pathogenic consequences may only become apparent with the eradication of WPV in sight. High-potency IPV and OPV were effective against the divergent WPV3 causing the 1984 Finland outbreak (summarized in ref.…”