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A new antigenic site of poliovirus recognized by an intertypic cross-neutralizing monoclonal antibody
J Uhlig1, K Wiegers, R Dernick
1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Federal Republic of Germany.
Abstract:
A monoclonal antibody (mAb 7J6) neutralizing poliovirus type 2 (PV2) and poliovirus type 1 (PV1) was obtained after immunization of BALB/c mice with infectious PV2, strain MEF-1. Preincubation of mAb 7J6 with PV1 inhibited its binding to PV2 and vice versa. Neutralization-resistant variants of PV2 and PV1 were selected. Nucleotide sequencing of the RNAs of some variants revealed mutations in the loop of amino acid residues 239 to 245 in VP2 and in the loop of amino acid residues 195 to 207 in VP3. This is the first evidence that these two loops contribute to a neutralization antigenic site (N-Ag) for poliovirus. Moreover, this new site on PV2 induced intertypic cross-neutralizing antibodies.
Insights
Researchers identified a new neutralization antigenic site on poliovirus by studying antibody resistance. This site on poliovirus type 2 induces cross-neutralizing antibodies against other poliovirus types.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Poliovirus poses a significant global health threat, necessitating ongoing research into viral neutralization mechanisms.
- Monoclonal antibodies are crucial tools for understanding viral structure and developing antiviral strategies.
Purpose of the Study:
- To characterize a novel neutralization antigenic site on poliovirus.
- To investigate the molecular basis of neutralization resistance in poliovirus.
Main Methods:
- Immunization of BALB/c mice with poliovirus type 2 (PV2) to generate monoclonal antibodies (mAbs).
- Selection and characterization of neutralization-resistant poliovirus variants (PV2 and PV1).
- Nucleotide sequencing of viral RNA to identify mutations in resistant variants.
Main Results:
- A monoclonal antibody, mAb 7J6, was identified that neutralizes both PV2 and poliovirus type 1 (PV1).
- Mutations in specific loops of VP2 (residues 239-245) and VP3 (residues 195-207) were found in neutralization-resistant variants.
- These findings provide the first evidence that these VP2 and VP3 loops constitute a neutralization antigenic site (N-Ag).
- This newly identified N-Ag on PV2 induced intertypic cross-neutralizing antibodies.
Conclusions:
- The study elucidates a novel neutralization antigenic site on poliovirus involving specific VP2 and VP3 loops.
- This site is critical for antibody recognition and neutralization.
- The induction of cross-neutralizing antibodies suggests potential for broader antiviral strategies.