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Journal of Virology, August 2000, p. 6800-6807, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antigenic Drift in the Influenza A Virus (H3N2) Nucleoprotein and Escape from Recognition by Cytotoxic T Lymphocytes

J. T. M. Voeten, T. M. Bestebroer, N. J. Nieuwkoop, R. A. M. Fouchier, A. D. M. E. Osterhaus, and G. F. Rimmelzwaan*

Institute of Virology and WHO National Influenza Centre, Erasmus Medical Centre Rotterdam, 3015 GE Rotterdam, The Netherlands

Received 19 January 2000/Accepted 20 March 2000

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.

* Corresponding author. Mailing address: Institute of Virology and WHO National Influenza Centre, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31-10-4088066. Fax: 31-10-4089485. E-mail: rimmelzwaan{at}viro.fgg.eur.nl.

Journal of Virology, August 2000, p. 6800-6807, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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