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.

, , , , , , , , , , ,
doi.org/10.1128/JVI.78.16.8946-8949.2004, hdl.handle.net/1765/13474
Journal of Virology
Erasmus MC: University Medical Center Rotterdam

Rimmelzwaan, G., Berkhoff, E., Nieuwkoop, N., Fouchier, R., & Osterhaus, A. (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