![]() b) (below) A new antigenic drift model, modified from Supplemental Fig.7 in reference ( Hensley et al., 2009).Īnti-HA antibodies neutralize the infectivity of influenza virus. Modified from Figure 1a in reference ( Shen et al., 2009b). Structure of H1N1 HA and a new antigenic drift model for HAĪ) (left) Structure of A/PR/8/34 H1N1 HA (PDB accession code 1RU7 Gamblin et al., 2004) highlighting the five antigenic sites: Sa (cyan), Sb (red), Ca1 (yellow), Ca2 (green), Cb (blue), using H3 HA numbering, and the receptor-binding site (labeled as 'RBS'). Combined with structural studies on influenza HA, it was found that the antigenic sites are located on the membrane-distal surface surrounding the receptor-binding site ( Figure 1a Wiley et al., 1981 Wilson et al., 1981). In general, HA proteins of influenza A virus have multiple antigenic sites, for instance, five for H1 (sites Sa, Sb, Ca1, Ca2 and Cb Figure 1a) and H3 (sites A~E) HA, six sites for H2 HA, 2~3 sites for H5 HA and two for H9 HA ( Caton et al., 1982 Gerhard et al., 1981 Kaverin et al., 2007 Kaverin et al., 2004 Kaverin et al., 2002 Tsuchiya et al., 2001 Underwood, 1982 Wiley et al., 1981). The locations of these natural mutations coincide with those of mutations found in escape variants that are often single amino-acid substitutions. Among them, the majority is located on the membrane-distal surface of HA 1. Although mutations on HA in field isolates can be found in both HA 1 and HA 2, at surface or buried locations, only those that are retained in viruses isolated in subsequent years may have carried advantages for re-infecting the same population ( Skehel and Wiley, 2000 Wiley and Skehel, 1987). Historically, the involvement of HA residues in antigenic drift has been demonstrated by mutations found in natural virus variants or escape variants selected by their ability to escape from neutralization by anti-HA monoclonal antibodies. ![]() This process, often referred to as 'antigenic drift', is most frequently observed on hemagglutinin (HA). This is largely due to the higher mutation rates in replication of its negative-stranded RNA genome by the RNA polymerase, followed by Darwinian selection for mutants with better ability to re-infect the same population. Influenza-virus caused infection remains a significant cause of morbidity and mortality worldwide.
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