Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations.
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Influenza A viruses accumulate amino acid substitutions in cytotoxic-T-lymphocyte (CTL) epitopes, allowing these viruses to escape from CTL immunity. The arginine-to-glycine substitution at position 384 of the viral nucleoprotein is associated with escape from CTLs. Introduction of the R384G substitution in the nucleoprotein gene segment of influenza virus A/Hong Kong/2/68 by site-directed mutagenesis was detrimental to viral fitness. Introduction of one of the comutations associated with R384G, E375G, partially restored viral fitness and nucleoprotein functionality. We hypothesized that influenza A viruses need to overcome functional constraints to accumulate mutations in CTL epitopes and escape from CTLs.
- Cell Line
- Research Support, Non-U.S. Gov't
- T-Lymphocytes, Cytotoxic/*immunology
- Mutagenesis, Site-Directed
- *Amino Acid Substitution
- *Epitopes, T-Lymphocyte/genetics/immunology
- Influenza A virus/*genetics/immunology/physiology
- RNA-Binding Proteins/genetics/immunology/*metabolism
- Viral Core Proteins/genetics/immunology/*metabolism