Dataset Information

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.

SUBMITTER: Ye J

PROVIDER: S-EPMC4161209 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ye Jianqiang J Xu Yifei Y Harris Jillian J Sun Hailiang H Bowman Andrew S AS Cunningham Fred F Cardona Carol C Yoon Kyoungjin J KJ Slemons Richard D RD Wan Xiu-Feng XF

Virology 20130904 1-2

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 189 ...[more]

PMID: 24074585

Similar Datasets

Project description:UnlabelledSwine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions.ImportanceInfluenza A virus (IAV) is an important pathogen in pigs and humans. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major target of vaccines. However, vaccine strains must be updated to reflect current strains. Characterizing the differences between seasonal IAV in humans and swine IAV is important in assessing the relative risk of interspecies transmission of viruses. We found two primary antigenic clusters of H3N2 in the U.S. pig population, with enough diversity to suggest updates in swine vaccine strains are needed. We identified changes in the HA protein that are likely responsible for these differences and that may be useful in predicting when vaccines need to be updated. The difference between human H3N2 viruses and those in swine is enough that population immunity is unlikely to prevent new introductions of human IAV into pigs or vice versa, reinforcing the need to monitor and prepare for potential introductions.

Project description:The continuous antigenic variation of influenza A viruses remains a major hurdle for vaccine selection; however, the molecular determinants and mechanisms of antigenic change remain largely unknown. In this study, two escape mutants were generated by serial passages of the Eurasian avian-like H1N1 swine influenza virus (EA H1N1 SIV) A/swine/Henan/11/2005 (HeN11) in the presence of two neutralizing monoclonal antibodies (mAbs) against the hemagglutinin (HA) protein, which were designated HeN11-2B6-P5 and HeN11-4C7-P8, respectively. The HeN11-2B6-P5 mutant simultaneously harbored the N190D and I230M substitutions in HA, whereas HeN11-4C7-P8 harbored the M269R substitution in HA (H3 numbering). The effects of each of these substitutions on viral antigenicity were determined by measuring the neutralization and hemagglutination inhibition (HI) titers with mAbs and polyclonal sera raised against the representative viruses. The results indicate that residues 190 and 269 are key determinants of viral antigenic variation. In particular, the N190D mutation had the greatest antigenic impact, as determined by the HI assay. Further studies showed that both HeN11-2B6-P5 and HeN11-4C7-P8 maintained the receptor-binding specificity of the parent virus, although the single mutation N190D decreased the binding affinity for the human-type receptor. The replicative ability in vitro of HeN11-2B6-P5 was increased, whereas that of HeN11-4C7-P8 was decreased. These findings extend our understanding of the antigenic evolution of influenza viruses under immune pressure and provide insights into the functional effects of amino acid substitutions near the receptor-binding site and the interplay among receptor binding, viral replication, and antigenic drift. IMPORTANCE The antigenic changes that occur continually in the evolution of influenza A viruses remain a great challenge for the effective control of disease outbreaks. Here, we identified three amino acid substitutions (at positions 190, 230, and 269) in the HA of EA H1N1 SIVs that determine viral antigenicity and result in escape from neutralizing monoclonal antibodies. All three of these substitutions have emerged in nature. Of note, residues 190 and 230 have synergistic effects on receptor binding and antigenicity. Our findings provide a better understanding of the functional effects of amino acid substitutions in HA and their consequences for the antigenic drift of influenza viruses.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets