A recommended numbering scheme for influenza A HA subtypes

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Comparative analysis of influenza virus subtypes is crucial for assessing zoonotic potential.
• Previous studies analyzed N-terminal cleavage sites for 13 influenza A hemagglutinin (HA) subtypes.
• Influenza A virus hemagglutinin (HA) is a key determinant of viral tropism and pathogenicity.

Purpose of the Study:

• To expand the comparative analysis of amino acid residues to all 18 known influenza A subtypes.
• To establish a standardized numbering system for structurally and functionally equivalent amino acids across all HA subtypes.
• To provide a list of amino acid equivalences known to influence viral phenotype.

Main Methods:

• Analysis of N-terminal cleavage sites across 18 influenza A hemagglutinin (HA) subtypes.
• Inclusion of diverse strains (multiple clades, high/low pathogenicity) for comprehensive comparison.
• Utilizing known structures of influenza A HA to define equivalent amino acids.

Main Results:

• A comprehensive analysis of amino acid residues across 18 influenza A HA subtypes was performed.
• A novel numbering system based on the mature HA sequence was established for cross-subtype comparisons.
• Equivalences for amino acids affecting viral phenotype were identified and listed.

Conclusions:

• The developed numbering system facilitates standardized comparisons of amino acid residues across diverse influenza A HA subtypes.
• This work enhances the understanding of structure-function relationships within influenza hemagglutinin.
• The findings contribute to assessing zoonotic potential and comparative studies of influenza virus strains.