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© Nadia Naffakh, Institut Pasteur
Immunofluorescence detection of influenza virus nucleoprotein in infected cells
Publication : Nucleic acids research

Codon conservation in the influenza A virus genome defines RNA packaging signals

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nucleic acids research - 01 Mar 2007

Gog JR, Afonso Edos S, Dalton RM, Leclercq I, Tiley L, Elton D, von Kirchbach JC, Naffakh N, Escriou N, Digard P

Link to Pubmed [PMID] – 17332012

Nucleic Acids Res. 2007;35(6):1897-907

Genome segmentation facilitates reassortment and rapid evolution of influenza A virus. However, segmentation complicates particle assembly as virions must contain all eight vRNA species to be infectious. Specific packaging signals exist that extend into the coding regions of most if not all segments, but these RNA motifs are poorly defined. We measured codon variability in a large dataset of sequences to identify areas of low nucleotide sequence variation independent of amino acid conservation in each segment. Most clusters of codons showing very little synonymous variation were located at segment termini, consistent with previous experimental data mapping packaging signals. Certain internal regions of conservation, most notably in the PA gene, may however signify previously unidentified functions in the virus genome. To experimentally test the bioinformatics analysis, we introduced synonymous mutations into conserved codons within known packaging signals and measured incorporation of the mutant segment into virus particles. Surprisingly, in most cases, single nucleotide changes dramatically reduced segment packaging. Thus our analysis identifies cis-acting sequences in the influenza virus genome at the nucleotide level. Furthermore, we propose that strain-specific differences exist in certain packaging signals, most notably the haemagglutinin gene; this finding has major implications for the evolution of pandemic viruses.

https://www.ncbi.nlm.nih.gov/pubmed/17332012