Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes.
Viruses exploit different strategies to escape immune surveillance, including the introduction of mutations in cytotoxic T-lymphocyte (CTL) epitopes. The sequence of these epitopes is critical for their binding to major histocompatibility complex (MHC) class I molecules and recognition by specific CTLs, both of which interactions may be lost by mutation. Sequence analysis of the nucleoprotein gene of influenza A viruses (H3N2) isolated in The Netherlands from 1989 to 1999 revealed two independent amino acid mutations at the anchor residue of the HLA-B27-specific CTL epitope SRYWAIRTR (383 to 391). A R384K mutation was found in influenza A viruses isolated during the influenza season 1989-1990 but not in subsequent seasons. In the influenza season 1993-1994, a novel mutation in the same CTL epitope at the same position was introduced. This R384G mutation proved to be conserved in all influenza A viruses isolated from 1993 onwards. Both mutations R384K and R384G abrogated MHC class I presentation and allowed escape from recognition by specific CTLs.
Voeten
J T
JT
Institute of Virology and WHO National Influenza Centre, Erasmus Medical Centre Rotterdam, 3015 GE Rotterdam, The Netherlands.
Bestebroer
T M
TM
Nieuwkoop
N J
NJ
Fouchier
R A
RA
Osterhaus
A D
AD
Rimmelzwaan
G F
GF
D000595:Amino Acid Sequence; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D010802:Phylogeny; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins