Abstract
Comparisons of residues between sub-types of influenza virus is increasingly used to assess the zoonotic potential of a circulating strain and for comparative studies across subtypes. An analysis of N-terminal cleavage sites for thirteen subtypes of influenza A hemagglutinin (HA) sequences, has previously been described by Nobusawa and colleagues. We have expanded this analysis for the eighteen known subtypes of influenza. Due to differences in the length of HA, we have included strains from multiple clades of H1 and H5, as well as strains of H5 and H7 subtypes with both high and low pathogenicity. Analysis of known structures of influenza A HA enables us to define amino acids which are structurally and functionally equivalent across all HA subtypes using a numbering system based on the mature HA sequence. We provide a list of equivalences for amino acids which are known to affect the phenotype of the virus.
Highlights
Amino acid changes in HA, resulting from either natural evolution or experimental design, are compared to amino acids within another subtype
The signal peptide contains a stretch of about 10 hydrophobic amino acids that have a tendency to form a single alpha-helix, albeit with little sequence conservation between subtypes
The length of the HA segment of influenza A shows substantial variation both between and within HA subtypes. This is caused by both changes in the length of the N-terminal signal peptide cleavage site and subtype specific amino acid insertions and deletions within the HA
Summary
Amino acid changes in HA, resulting from either natural evolution or experimental design, are compared to amino acids within another subtype. As shown for H7, the conversion of residue numbering between subtypes varies depending on the region of HA being compared Another complication arises due to genetic changes within a subtype which, uncommon, do occur. Over one-fifth of the avian H5N1 strains in the Middle East sequenced to date have a deletion between amino acids positions 128 and 130 (mature HA H5N1 numbering). This deletion was found in human seasonal H1 strains after 1995 but was not present in early H1 strains or any of the H1pdm strains currently circulating [3]. Conversion rules depend upon the lineage of the subtypes that are being compared
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