Figure 1.
Comparison of the structures of antigenic sites on the HA molecules among 1918 H1N1 (SC1918), recent seasonal H1N1 (BR2007), and 2009 H1N1 (CA2009).
Three-dimensional models of the H1 HA molecules of SC1918, BR2007, and CA2009 were constructed based on the HA crystal structures of A/South Carolina/1/18, A/Puerto Rico/8/34, and A/swine/Iowa/30, respectively (PDB codes: 1RUZ, 1RU7, and 1RUY, respectively). Models with solvent-accessible surface representation were generated by a molecular modeling method as described in the Methods section. Molecular surface of the HA trimers viewed on its side (upper) and top (lower) are shown (A). One monomer (center) is colored gray and the others are colored dark gray. The antigenic sites, Sa (light pink), Sb (light blue), Ca (pale green), and Cb (light orange) are indicated on the model of SC1918 HA. The spatial locations of amino acid residues that are distinct from those of SC1918 HA are shown in red on the models of BR2007 and CA2009 HAs. Each amino acid residue is mapped on the close-up views of each antigenic site of SC1918, BR2007, and CA2009 HAs (B). The Ca site is divided into subregions, Ca1 and Ca2. Amino acids are colored by the default ClustalX color scheme [29]: Trp, Leu, Val, Ile, Met, Phe, and Ala (blue); Lys and Arg (red); Thr, Ser, Asn, and Gln (green); Cys (pink); Asp and Glu (magenta); Gly (orange); His and Tyr (cyan); Pro (yellow).
Table 1.
Amino acid similarity in the HA antigenic sites among recent seasonal H1N1 (BR2007), 2009 H1N1 (CA2009), and 1918 H1N1 (SC1918).
Figure 2.
Amino acid substitutions associated with antigenic changes of seasonal human H1N1 virus HAs.
All models were generated and shown by a molecular modeling method as described in the Methods section and the legend of Figure 1.
Figure 3.
Comparison of the N-glycosylation potential of HA between SC1918 and CA2009.
Residues shown in green represent Asn at the actually existing N-glycosylation sites. Residues shown in orange or blue represent the amino acids in Cand1 sites that require a nucleotide substitution to produce N-glycosylation sites. Residues shown in blue represent the amino acids that were actually substituted, resulting in the acquisition of N-glycosylation sites during the antigenic evolution of human H1N1 viruses. Numbers in parentheses show the positions of Asn residues that may be linked to carbohydrate chains, if respective Cand1 sites mutate to have N-glycosylation sites. All models were generated as described in the Methods section and the legend of Figure 1.
Figure 4.
Prediction of the future amino acid substitutions on the antigenic sites of 2009 H1N1 HA.
Amino acid sequences of HA antigenic sites of human H1N1 viruses are shown. Sequence data are corresponding to those of virus strains shown in Figures 1 and 2. Amino acid residues shared between 1918 H1N1 (SC1918) and 2009 H1N1 (CA2009) are shown in red, and those that have been substituted since 1934 are shown in blue. Amino acid residues indicated by arrows represent the predicted substitutions which might be associated with antigenic changes of 2009 H1N1 in the near future. The amino acid substitutions which have already been found in the recent variants of the 2009 H1N1 virus (as of November 3, 2009) are shown in bold pink letters.