Mutation from arginine to lysine at the position 189 of hemagglutinin contributes to the antigenic drift in H3N2 swine influenza viruses

Abstract

Two distinct antigenic clusters were previously identified among the H3N2 swine influenza A viruses (IAVs) and were designated H3N2SIV-alpha and H3N2SIV-beta (Feng et al., 2013. Journal of Virology 87 (13), 7655-7667). A consistent mutation was observed at the position 189 of hemagglutinin (R189K) between H3N2SIV-alpha and H3N2SIV-beta fair isolates. To evaluate the contribution of R189K mutation to the antigenic drift from H3N2SIV-alpha to H3N2SIV-beta, four reassortant viruses with 189R or 189K were generated. The antigenic cartography demonstrated that the R189K mutation in the hemagglutinin of H3N2 IAV contributed to the antigenic drift, separating these viruses into H3N2SIV-alpha to H3N2SIV-beta. This R189K mutation was also found to contribute to the cross-reaction with several ferret sera raised against historical human IAVs with hemagglutinin carrying 189K. This study suggests that the R189K mutation plays a vital role in the antigenicity of swine and human H3N2 IAVs and identification of this antigenic determinant will help us rapidly identify antigenic variants in influenza surveillance.

Keywords: Antigenic cartography; Antigenic drift; Antigenic variant; H3N2; H3N2v; Influenza A virus; R189K; Serological assay.

Figure 1

Antigenic cartography was constructed using HI data for 68 SIV isolates from Ohio agricultural fairs (2009-2011),12 SIV isolates from commercial farms (2006-2012), and four human H3N2v influenza virus isolates, and four reassortant viruses (09SW64_189R, 09SW64_189K, 11SW347_189R, and 11SW347_189K). The HI data for 80 SIV isolates and four human H3N2v isolates were adapted from (Feng et al., 2013), and those for four reassortant viruses were shown in Table 1. Antigenic clusters H3N2SIV-alpha and H3N2SIV-beta and the viruses in each clusters were described in (Feng et al., 2013). 09SW64 and the corresponding reassortants (09SW64_189R and 09SW64_189K) were marked in blue whereas 11SW347 and the corresponding reassortants (11SW347_189R and 11SW347_189K) in pink. This cartography demonstrates that R189K moves 09SW64 from antigenic cluster H3N2SIV-alpha towards H3N2SIV-beta and that K189R moves 11SW347 from antigenic cluster H3N2SIV-beta towards H3N2SIV-alpha. Antigenic cartography was constructed using AntigenMap (http://sysbio.cvm.msstate.edu/AntigenMap) (Barnett et al., 2012; Cai, Zhang, and Wan, 2010).