Large-scale sequence analysis of hemagglutinin of influenza A virus identifies conserved regions suitable for targeting an anti-viral response.
BACKGROUND
Influenza A viral surface protein, hemagglutinin, is the major target of neutralizing antibody response and hence a main constituent of all vaccine formulations. But due to its marked evolutionary variability, vaccines have to be reformulated so as to include the hemagglutinin protein from the emerging new viral strain. With the constant fear of a pandemic, there is critical need for the development of anti-viral strategies that can provide wider protection against any Influenza A pathogen. An anti-viral approach that is directed against the conserved regions of the hemaggutinin protein has a potential to protect against any current and new Influenza A virus and provide a solution to this ever-present threat to public health.


RESULTS
Influenza A human hemagglutinin protein sequences available in the NCBI database, corresponding to H1, H2, H3 and H5 subtypes, were used to identify highly invariable regions of the protein. Nine such regions were identified and analyzed for structural properties like surface exposure, hydrophilicity and residue type to evaluate their suitability for targeting an anti-peptide antibody/anti-viral response.


CONCLUSIONS
This study has identified nine conserved regions in the hemagglutinin protein, five of which have the structural characteristics suitable for an anti-viral/anti-peptide response. This is a critical step in the design of efficient anti-peptide antibodies as novel anti-viral agents against any Influenza A pathogen. In addition, these anti-peptide antibodies will provide broadly cross-reactive immunological reagents and aid the rapid development of vaccines against new and emerging Influenza A strains.
Sahini
Leepakshi
L
Department of Process and Analytical Biochemistry, ChimericBio Incorporated, Long Island City, New York, United States of America.
Tempczyk-Russell
Anna
A
Agarwal
Ritu
R
D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D017124:Conserved Sequence / Q000235:genetics / Q000276:immunology*; D030561:Databases, Nucleic Acid; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA / Q000379:methods
D000906:Antibodies; D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus