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Journal of Virology, August 2004, p. 8946-8949, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8946-8949.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Functional Compensation of a Detrimental Amino Acid Substitution in a Cytotoxic-T-Lymphocyte Epitope of Influenza A Viruses by Comutations

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

Department of Virology and WHO National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands

Received 19 January 2004/ Accepted 8 April 2004

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.

* Corresponding author. Mailing address: Erasmus MC, Department of Virology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31-104088243. Fax: 31-104089485. E-mail: g.rimmelzwaan{at}erasmusmc.nl.

Journal of Virology, August 2004, p. 8946-8949, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8946-8949.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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