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Characterization of host cell binding variants of influenza virus by monoclonal antibodies
Abstract:
We have previously shown that a plaque-type mutant of influenza virus A/WSN has a growth advantage in MDBK cells because its hemagglutinin (HA) has a greater affinity for host cell receptors than does the HA of the parent virus. We show here that the mutant is also less sensitive than the parent to neutralization by antibodies to epitopes in at least two regions on the HA. WSN-specific monoclonal antibodies which had higher radioimmunoassay (RIA) titers against the parent than the mutant virus also had higher plaque inhibition (PI) and hemagglutination inhibition (HI) titers. In contrast, cross-reacting antibodies bound equally well to the parent and mutant viruses as judged by RIA but those which bound to the Cb region of the HA exhibited higher PI and HI titers against the parent virus. The results suggest that preferential neutralization of the parental virus by antibodies can contribute to the selective advantage of mutants which have increased affinity for cellular receptors.
Insights
Influenza virus mutants with higher receptor affinity show reduced sensitivity to antibody neutralization. This suggests that antibody evasion contributes to the selective advantage of these viral mutants.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Influenza virus A/WSN plaque-type mutants exhibit enhanced growth in MDBK cells due to higher hemagglutinin (HA) affinity for host cell receptors compared to the parent virus.
- Antibody neutralization is a key host defense mechanism against viral infections.
Purpose of the Study:
- To investigate the sensitivity of an influenza virus mutant with increased HA receptor affinity to antibody neutralization.
- To determine if altered antibody binding contributes to the selective advantage of such mutants.
Main Methods:
- Radioimmunoassay (RIA) was used to assess antibody binding to parent and mutant viruses.
- Plaque inhibition (PI) and hemagglutination inhibition (HI) assays were performed to evaluate the functional neutralization capacity of antibodies.
- Monoclonal antibodies specific to WSN virus and cross-reacting antibodies targeting different HA regions were employed.
Main Results:
- The mutant virus demonstrated reduced sensitivity to neutralization by antibodies targeting at least two HA regions compared to the parent virus.
- WSN-specific monoclonal antibodies showed higher RIA, PI, and HI titers against the parent virus than the mutant.
- Cross-reacting antibodies exhibited similar binding (RIA) to both viruses, but those targeting the Cb region showed higher PI and HI titers against the parent virus.
Conclusions:
- Mutants with increased HA receptor affinity are less susceptible to antibody-mediated neutralization.
- Preferential neutralization of the parental virus by antibodies can contribute to the selective advantage of viral mutants with enhanced receptor binding.
- These findings highlight the interplay between viral receptor binding, antibody evasion, and viral evolution.