Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites.
In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site. The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu), zanamivir (Relenza) and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuraminidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients.


METHODS
This article was reviewed by Sandor Pongor and L. Aravind.
Maurer-Stroh
Sebastian
S
Biomolecular Function Discovery Division, Bioinformatics Institute (BII), Agency for Science Technology and Research (A*STAR), Singapore. sebastianms@bii.a-star.edu.sg
Ma
Jianmin
J
Lee
Raphael Tze Chuen
RT
Sirota
Fernanda L
FL
Eisenhaber
Frank
F
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D017124:Conserved Sequence; D014644:Genetic Variation / Q000187:drug effects; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D010802:Phylogeny; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D013499:Surface Properties / Q000187:drug effects
D000914:Antibodies, Viral; D000998:Antiviral Agents; D009439:Neuraminidase