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Antigen distortion allows influenza virus to escape neutralization
D Fleury1, S A Wharton, J J Skehel
1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Gif-sur-Yvette, France.
Nature Structural Biology
|February 14, 1998
Summary
A mutant influenza virus hemagglutinin (HA) mutation avoids unfavorable structures to escape antibodies. Interestingly, the antibody binds to a distorted HA conformation, offering a new escape mechanism.
Area of Science:
- Virology
- Structural Biology
- Immunology
Background:
- Influenza virus hemagglutinin (HA) is a key target for neutralizing antibodies.
- Viruses can escape antibody neutralization through various mechanisms, including mutations in viral proteins.
Purpose of the Study:
- To investigate the structural basis of antibody escape in a mutant influenza virus.
- To understand how mutations in hemagglutinin affect its conformation and antibody binding.
Main Methods:
- X-ray crystallography was used to determine the structure of the mutant hemagglutinin (HA) and its complex with a monoclonal antibody Fab fragment.
- Structural analysis was performed to compare the wild-type and mutant HA conformations and their interactions with the antibody.
Main Results:
- The mutation in the influenza virus HA confers resistance to antibody neutralization by avoiding an energetically unfavorable conformation.
- Structural analysis revealed that the antibody selectively binds to the mutant HA in a conformation resembling the wild-type, despite the mutation's effect.
- This binding to a less favored conformation represents a novel mechanism for viral escape from antibody neutralization.
Conclusions:
- Mutations in influenza HA can lead to antibody escape through conformational changes.
- Antibodies can adapt to bind altered viral structures, even less energetically favorable ones.
- This study presents a new paradigm for viral immune evasion strategies.