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.
|Keywords||*Antigenic Variation, *Influenza A Virus, H3N2 Subtype, *RNA-Binding Proteins, Amino Acid Sequence, Antigens, Viral/immunology, Epitopes, T-Lymphocyte, HLA-B27 Antigen/immunology, Humans, Influenza A virus/genetics/*immunology/isolation & purification, Influenza, Human/virology, Molecular Sequence Data, Mutation, Nucleoproteins/chemistry/*genetics/*immunology/metabolism, Phylogeny, Research Support, Non-U.S. Gov't, T-Lymphocytes, Cytotoxic/*immunology, Viral Core Proteins/chemistry/*genetics/*immunology/metabolism|
Bestebroer, T.M., Nieuwkoop, N.J., Fouchier, R.A.M., Rimmelzwaan, G.F., Voeten, J.T.M., & Osterhaus, A.D.M.E.. (2000). Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. Journal of Virology. Retrieved from http://hdl.handle.net/1765/9409