Antigenic Variation and Resistance to Neutralization in Poliovirus Type 1

Diamond, David C.; Jameson, Bradford A.; Bonin, Jutta; Kohara, Michinori; Abe, S.; Itoh, Hidenori; Komatsu, Toshihiko; Arita, Masataka; Kuge, Shusuke; Nomoto, Akio; Osterhaus, Albert D. M. E.; Crainic, R; Wimmer, Eckard

doi:10.1126/science.2412292

Cited by 122 publications

(94 citation statements)

References 33 publications

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“…The same is not true for the remaining three antibodies, and it is possible that each of the amino acid substitutions conferring resistance to AP7, API2 and LP2 occurs at some distance from the corresponding antibody binding site, but modifies the site by allosteric effects within the molecule. Mutations that confer antibody resistance by long-range effects have been observed in poliovirus (Diamond et al, 1985) and tobacco mosaic virus (A1 Moudallal et al, 1982), but in these instances protein-protein interactions play an important part in determining the secondary and tertiary structure of individual subunits. It seems unlikely that mutations could act at long range (i.e.…”

Section: Discussionmentioning

confidence: 99%

An Analysis of the Biological Properties of Monoclonal Antibodies against Glycoprotein D of Herpes Simplex Virus and Identification of Amino Acid Substitutions that Confer Resistance to Neutralization

Minson

Hodgman

Digard

et al. 1986

Journal of General Virology

179

183

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SUMMARYFour monoclonal antibodies to glycoprotein D (gD) of herpes simplex virus (HSV) types 1 and 2 neutralized virus in the presence of complement but exhibited diverse activities in its absence. Amino acid substitutions that conferred resistance to neutralization by each antibody were identified by deriving the nucleotide sequence of the gD gene from resistant mutants. Each antibody selected a substitution from different parts of the molecule and mutants resistant to a single antibody always arose from the same mutation. One of the antibodies reacted with a synthetic oligopeptide corresponding to the region of the molecule in which amino acid substitution conferred resistance, but the remaining three antibodies failed to react with predicted oligopeptide targets. These antibodies may therefore react with 'discontinuous' epitopes, a view supported by the observation that two of these three antibodies competed with each other in binding assays despite the fact that substitutions conferring resistance to neutralization arose nearly 100 residues apart in the primary sequence. The four antibodies had very different biological properties. One antibody neutralized infectivity but did not inhibit cell fusion, one antibody inhibited cell fusion but did not neutralize, while a third antibody had both activities. One antibody had neither activity but enhanced the infectivity of HSV-2 in a type-specific manner. The ability of antibodies to inhibit cell fusion by syncytial virus strains correlated with an ability to prevent plaque enlargement by a non-syncytial virus strain, implying a role for gD in the intercellular spread of virus that is independent of the syncytial phenotype. We found no correlation between neutralizing activity and anti-fusion activity suggesting that, while gD is involved in cell fusion, it has at least one other function which is required for infectivity.

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Section: Discussionmentioning

confidence: 99%

An Analysis of the Biological Properties of Monoclonal Antibodies against Glycoprotein D of Herpes Simplex Virus and Identification of Amino Acid Substitutions that Confer Resistance to Neutralization

Minson

Hodgman

Digard

et al. 1986

Journal of General Virology

179

183

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“…In contrast, frequencies of resistance to monoclonal antibody neutralization for poliovirus are in the range 10-3 to 10-5 base substitutions per site (29,30). In vitro measurements of poliovirus polymerase error frequencies (31) and the mutation frequency of poliovirus type 1 to a high degree of resistance to guanidine indicated specific single-site mutation frequencies for poliovirus of the order of 10-3 to 10-4 (32,33).…”

mentioning

confidence: 98%

High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.

Torre

Giachetti

Semler

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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We employed independent clones of a temperature-sensitive mutant of type 1 poliovirus, to quantitate the frequency of specific U -+ C transitions at nucleotide 5310, within the genomic region encoding polypeptide 3AB, which is involved in the initiation ofRNA replication.Only this U --C base substitution restores the wild-type phenotypic ability to form plaques at 39C; the other two base substitutions at this site are lethal. The observed frequency of this specific transition averaged 2 x i0S, and all revertant viruses forming plaques at39°C contained the expected cytidine at nucleotide 5310. Incredibly, only 3 of 10 revertants exhibited this one specific U --C transition whereas 7 of 10 exhibited this same transition plus four additional base substitutions that precisely reverted temperature-sensitive 3AB-310/4 to wildtype poliovirus sequence (these latter four mutations had been introduced into 3AB-310/4 as silent third base mutations to provide new restriction sites in infectious cDNAs). No other mutations were detected in this polypeptide 3AB domain in either the single-base or the precise 5-base revertants. No intermediates were seen; all revertants exhibited either the single U --C transition at nucleotide 5310 or the same transition plus four precise reversions to the wild-type sequence at sites 8, 11, 43, and 46 bases distant from nucleotide 5310. Similar results were obtained after transfection of cDNAderived transcripts. We discuss possible mechaniss for our data. These include (but may not be limited to) error-prone polymerase activity, sequential RNA recombination events joining independent mutations, or some unusual RNA editing process.Considerable data now document the extensive genetic variability and potential for rapid evolution of RNA viruses (1-19). The molecular basis for this variation is extremely high mutation frequencies per average site in RNA virus genomes (ranging between 10-3 and 10-6 and usually of the order of 10' to 10-5). Such high mutation frequencies dictate that even clones of RNA viruses are not homogeneous populations but consist of complex "mutant swarms" or "quasispecies" populations (20)(21)(22)(23)(24)(25)(26). By virtue of their extreme heterogeneity, quasispecies populations can adapt rapidly to new environments by selection of variants preexisting within the population. Some very low polymerase error values have been reported for poliovirus. Thus, Parvin et al. (27) have estimated a poliovirus mutation rate of <10-6 per site for viable neutral or quasineutral mutants of poliovirus.A similar low error frequency of 2.5 x 10-6 was estimated for the reversion of a poliovirus amber mutant (28). In contrast, frequencies of resistance to monoclonal antibody neutralization for poliovirus are in the range 10-3 to 10-5 base substitutions per site (29,30). In vitro measurements of poliovirus polymerase error frequencies (31) and the mutation frequency of poliovirus type 1 to a high degree of resistance to guanidine indicated specific single-site mutation frequencies...

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“…However the results reported here imply that antibodies may appear to react with peptide sequences which are not recognized in the native antigen and that little of the peptide may be in the appropriate conformation to induce cross-reactive antibodies. Emini et al (1983) used the reactions of monoclonal antibodies with synthetic peptides to identify antigenic sites on type 1 poliovirus and these studies led to the conclusion that mutations were frequently located outside the antibody-binding site (Diamond et al, 1985;Blondel et al, 1986). However this conclusion is difficult to reconcile with the three-dimensional structure of type 1 poliovirus (Hogle et al, 1985).…”

Section: Sa/37 a I I E V D N E Q P T T R A Q K L F A M W R I S10 E mentioning

confidence: 99%

Reactivity of Anti-peptide and Anti-poliovirus Type 3 Monoclonal Antibodies with Synthetic Peptides

Ferguson

Reed

Minor

1986

Journal of General Virology

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SUMMARYMonoclonal antibodies were prepared from mice immunized with an 18-residue synthetic peptide with an amino acid sequence from a major antigenic sequence involved in the neutralization of type 3 poliovirus. Approximately 250 hybridomas secreted antibodies that reacted with the peptide but not the virus, two antibodies reacted with the virus but not the peptide and no antibody reacted with both. Conversely 26 monoclonal antibodies prepared from mice immunized with type 3 poliovirus and known to be directed against the appropriate sequence on the virus, generally failed to react with the peptide. These results might be expected if only a small proportion of the free or coupled peptide molecules adopt molecular conformations which resemble that of the homologous antigenic site in the virus. Antibodies specific for other antigens occasionally reacted well with the synthetic peptides, indicating that antibodies may bind to peptides of inappropriate sequence. The identification of antigenic sites by the use of synthetic peptides therefore requires considerable caution.We have used indirect biological methods to identify antigenic sites involved in the neutralization of type 3 poliovirus Evans et al., 1983). Three sites have been identified, an immunodominant site at amino acids 89 to 100 on VP1, a site on VP2 and a complex site composed of residues from VP3 and VP1 . These findings are consistent with the published X-ray crystallographic structure of poliovirus (Hogle et al., 1985) and with studies using polyclonal sera ). Other workers have used different approaches to identify antigenic sites on type 1 poliovirus. These include cross-linking of monoclonal antibodies to the virus (Emini et al., 1982), the induction of neutralizing antibodies by synthetic peptides (Chow et al., 1985) and the binding of neutralizing monoclonal antibodies to a VPl-fl-lactamase fusion protein (Van der Werf et al., 1983). In addition the ability of monoclonal or polyclonal antibodies to bind to synthetic peptides in direct ELISA has been used as a criterion for the identification of important antigenic sites in poliovirus type 1 (Emini et al., 1983), hepatitis B virus (Neurath et al., 1984) and Epstein-Barr virus (Dillner et al., 1984) and has been suggested as a general method (Geyson et al., 1984). We have therefore examined the immunological properties of synthetic peptides whose sequences were based on the known immunodominant site of type 3 poliovirus. The findings suggest that the binding of antibodies to synthetic peptides in direct ELISA cannot be regarded as a universally valid approach, and that the results of such studies should be interpreted with caution.The peptides used in these studies were synthesized by the Fmoc-polyamide method (Cambridge Research Biochemicals, Cambridge, U.K. ; Brown et al., 1983) and their sequences are given in Table 1. Synthetic peptide S10a, which contains the amino acid sequence of the major antigenic site on VP 1 of the Sabin vaccine strain of type 3 poliovirus, has been shown to induce ty...

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Antigenic Variation and Resistance to Neutralization in Poliovirus Type 1

Cited by 122 publications

References 33 publications

An Analysis of the Biological Properties of Monoclonal Antibodies against Glycoprotein D of Herpes Simplex Virus and Identification of Amino Acid Substitutions that Confer Resistance to Neutralization

An Analysis of the Biological Properties of Monoclonal Antibodies against Glycoprotein D of Herpes Simplex Virus and Identification of Amino Acid Substitutions that Confer Resistance to Neutralization

High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.

Reactivity of Anti-peptide and Anti-poliovirus Type 3 Monoclonal Antibodies with Synthetic Peptides

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