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Published on: October 7, 2011
Characterization of Mengo virus neutralization epitopes. II. Infection of mice with an attenuated virus
Abstract:
A panel of five neutralizing monoclonal antibodies was generated from mice immunized with an attenuated strain of Mengo virus. Four of the antibodies were used to select mutants of Mengo virus which were able to escape neutralization by the selecting antibody, but it was not possible to select mutants which could escape neutralization by the fifth antibody. The capsid coding region of the RNA genome of each mutant was directly sequenced to identify the mutation(s) responsible for the neutralization escape phenotype. These results are compared to those of a previous study in which immunogenic determinants recognized by neutralizing antibodies generated against pentameric capsid subunits were located on the external surface of the Mengo virion. We have confirmed the existence of the previously identified immunogenic determinant in VP3 (site 2) as well as an immunodominant determinant in VP2 (site 1). Two previously uncharacterized determinants, located in surface loops of VP1 (sites 3 and 4A), were also identified. None of the mutations conferring the neutralization escape phenotype was found near the surface depressions on the virion which are believed to be the receptor binding sites.
Insights
Researchers identified new neutralization escape sites on the Mengo virus capsid. These findings map key regions of the virus, aiding in understanding viral evolution and antibody interactions.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Mengo virus neutralization is mediated by antibodies targeting specific viral proteins.
- Understanding these interactions is crucial for developing antiviral strategies.
Purpose of the Study:
- To identify and characterize novel neutralization escape mutants of Mengo virus.
- To map the immunogenic determinants on the Mengo virus capsid recognized by neutralizing antibodies.
Main Methods:
- Generation of neutralizing monoclonal antibodies against Mengo virus.
- Selection and sequencing of Mengo virus neutralization escape mutants.
- Comparison of mutation sites with previously identified immunogenic determinants.
Main Results:
- Four of five monoclonal antibodies selected for neutralization escape mutants.
- Confirmed previously identified determinant in VP3 (site 2) and dominant determinant in VP2 (site 1).
- Identified two new determinants in VP1 surface loops (sites 3 and 4A).
- Escape mutations were not located near putative receptor binding sites.
Conclusions:
- Novel neutralization-resistant epitopes on the Mengo virus capsid have been characterized.
- These findings contribute to the understanding of viral immune evasion mechanisms.
- The identified sites offer potential targets for future antiviral drug development.
