Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations.
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.
|Keywords||*Amino Acid Substitution, *Epitopes, T-Lymphocyte/genetics/immunology, Cell Line, Humans, Influenza A virus/*genetics/immunology/physiology, Mutagenesis, Site-Directed, Mutation, Nucleoproteins/genetics/immunology/*metabolism, RNA-Binding Proteins/genetics/immunology/*metabolism, Research Support, Non-U.S. Gov't, T-Lymphocytes, Cytotoxic/*immunology, Viral Core Proteins/genetics/immunology/*metabolism|
|Note||Free full text at PubMed|
|Persistent URL||dx.doi.org/10.1128/JVI.78.16.8946-8949.2004, hdl.handle.net/1765/13474|
Rimmelzwaan, G.F., Berkhoff, E.G.M., Nieuwkoop, N.J., Fouchier, R.A.M., & Osterhaus, A.D.M.E.. (2004). Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations.. Journal of Virology, 78(16), 8946–8949. doi:10.1128/JVI.78.16.8946-8949.2004