Antigenic structure of influenza A virus hemagglutinin
The hemagglutinin of influenza virus is a highly variable surface glycoprotein. 17 antigenic subtypes of the influenza A virus hemagglutinin have been described. The hemagglutinin is the primary target of virus-neutralizing antibodies. The location and structure of the antigenic sites in the hemagglutinin molecule of the influenza A virus H3 subtype were revealed three decades ago. Later the antigenic sites of H1 and H2 subtypes were mapped with the use of the H3 three-dimensional model, the only one available at the time. Preliminary data on the location of antigenic sites of the H5 hemagglutinin were also presented. After the X-ray crystallographic structures of the H5 and H9 hemagglutinins were reported, we performed the mapping of the antigenic structure of the H5 and H9 hemagglutinins in greater detail. The virus mutants resistant to monoclonal antibodies (escape mutants) were selected and used in immune cross-reactions with the monoclonal antibodies. The mutant hemagglutinin genes were sequenced, and the location of the antigenically relevant amino acid residues in the three-dimensional structure of the hemagglutinin molecule was determined. For the H5 subtype two antigenic sites analogous to sites A and B of the H3 subtype were revealed at the lateral loop and at the distal end of the hemagglutinin globule. After the appearance and spread of the highly pathogenic H5N1 influenza virus we performed the antigenic mapping of its hemagglutinin. The mapping revealed a rapid evolution of the antigenic structure of the H5 hemagglutinin. This conclusion was confirmed by the analysis of amino acid positions recognized by monoclonal antibodies against A/duck/Novosibirsk/56/05 (H5N1) influenza virus isolated at the Virus Ecology Department of the D.I. Ivanovsky Institute of Virology and belonging to the Qinghai-Siberian variant having spread in Western Siberia, Europe, Africa and Middle East. The H9 hemagglutinin was shown to differ sharply from any subtype analyzed so far, since it did not contain an antigenic site corresponding to site A in the H3 subtype. After the appearance and spread of the pandemic 2009 influenza H1N1 virus, we mapped the amino acid positions recognized by the monoclonal antibodies against the strain A/IIVMoscow/01/09 (H1N1) pdm09, the first strain of the pandemic 2009 virus isolated in Russia at the Virus Ecology Department of the D.I. Ivanovsky Institute of Virology. The amino acid changes in the hemaglutinin of the escape mutants occurred in a limited area of the hemagglutinin globule, and they induced a decrease of the hemagglutinin affinity to the sialic analogs of cell receptors, which may explain a limited range of antigenic drift of the 2009 pandemic virus.