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.
Erasmus MC, Department of Virology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. g.rimmelzwaan@erasmusmc.nl
G F
GF
Rimmelzwaan
E G M
EG
Berkhoff
N J
NJ
Nieuwkoop
R A M
RA
Fouchier
A D M E
AD
Osterhaus
D019943:Amino Acid Substitution; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins