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Bioinformatics Advance Access published online on November 7, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl559
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© 2006 The Author(s)
Received August 19, 2006
Revised October 11, 2006
Accepted October 31, 2006

Discovery note

An RNA conformational shift in recent H5N1 influenza A viruses

Alexander P. Gultyaev 1, Hans A. Heus 2, and René C. L. Olsthoorn 3 *

1 Leiden Institute of Biology, Leiden University, P.O.Box 9516, 2300 RA Leiden, The Netherlands
2 Institute for Molecules and Materials, Department of Biophysical Chemistry, Radboud University Nijmegen, P.O.Box 9010, 6500 GL Nijmegen, The Netherlands
3 Leiden Institute of Chemistry, Leiden University, P.O.Box 9502, 2300 RA Leiden, The Netherlands


  Abstract

Recent outbreaks of avian influenza are being caused by unusually virulent H5N1 strains. It is unknown what makes these recent H5N1 strains more aggressive than previously circulating strains. Here, we have compared more than 3000 RNA sequences of segment 8 of type A influenza viruses and found a unique single nucleotide substitution typically associated with recent H5N1 strains. By phylogenetic analysis, biochemical and biophysical experiments, we demonstrate that this substitution dramatically affects the equilibrium between a hairpin and a pseudoknot conformation near the 3' splice site of the NS gene. This conformational shift may have consequences for splicing regulation of segment 8 mRNA. Our data suggest that besides changes at the protein level, changes in RNA secondary structure should be seriously considered when attempting to explain influenza virus evolution.

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Martin Bishop
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