tetano
Editor, Senior Moderator
J Gen Virol. 2014 Feb 14. doi: 10.1099/vir.0.061598-0. [Epub ahead of print]
Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus hemagglutinin (HA).
Garc?a-Barreno B, Delgado T, Benito S, Casas I, Pozo F, Cuevas MT, Mas V, Trento A, Rodriguez-Frandsen A, Falcon A, Ortin J, Nieto A, Melero JA.
Author information
Abstract
Murine hybridomas producing neutralizing monoclonal antibodies (MAbs) specific of the pandemic influenza virus A/Cal/07/09 hemagglutinin (HA) were isolated. These antibodies recognized at least two different but overlapping new epitopes that were conserved in the HA of most Spanish pandemic isolates. However, one of these isolates (A/Extr/6530/10) lacked reactivity with the monoclonals and carried two unique mutations in the HA head (S88Y and K136N) that were required simultaneously to ablate reactivity with the murine antibodies. This unusual requirement directly illustrates the phenomenon of enhanced antigenic change proposed for the accumulation of simultaneous amino acid substitutions at antigenic sites of the influenza A virus hemagglutinin during virus evolution (Shih et al., Proc. Nal. Acad. Sci. USA, 104:6283-6288, 2007). The changes found in the A/Extr/6530/10 HA were not found in escape mutants selected in vitro with one of the monoclonals, which contained instead nearby single amino acid changes in the HA head. Thus, either single or double point mutations may alter similarly epitopes of the new antigenic site identified in this work on the 2009 H1N1 pandemic virus HA. Moreover, this site is relevant for the human antibody response, as shown by competition of MAbs and human postinfection sera for virus binding. The results are discussed in the context of the HA antigenic structure and challenges posed for identification of sequence changes with possible antigenic impact during virus surveillance.
KEYWORDS:
antigenicity, hemagglutinin, influenza
PMID:
24531414
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24531414
Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus hemagglutinin (HA).
Garc?a-Barreno B, Delgado T, Benito S, Casas I, Pozo F, Cuevas MT, Mas V, Trento A, Rodriguez-Frandsen A, Falcon A, Ortin J, Nieto A, Melero JA.
Author information
Abstract
Murine hybridomas producing neutralizing monoclonal antibodies (MAbs) specific of the pandemic influenza virus A/Cal/07/09 hemagglutinin (HA) were isolated. These antibodies recognized at least two different but overlapping new epitopes that were conserved in the HA of most Spanish pandemic isolates. However, one of these isolates (A/Extr/6530/10) lacked reactivity with the monoclonals and carried two unique mutations in the HA head (S88Y and K136N) that were required simultaneously to ablate reactivity with the murine antibodies. This unusual requirement directly illustrates the phenomenon of enhanced antigenic change proposed for the accumulation of simultaneous amino acid substitutions at antigenic sites of the influenza A virus hemagglutinin during virus evolution (Shih et al., Proc. Nal. Acad. Sci. USA, 104:6283-6288, 2007). The changes found in the A/Extr/6530/10 HA were not found in escape mutants selected in vitro with one of the monoclonals, which contained instead nearby single amino acid changes in the HA head. Thus, either single or double point mutations may alter similarly epitopes of the new antigenic site identified in this work on the 2009 H1N1 pandemic virus HA. Moreover, this site is relevant for the human antibody response, as shown by competition of MAbs and human postinfection sera for virus binding. The results are discussed in the context of the HA antigenic structure and challenges posed for identification of sequence changes with possible antigenic impact during virus surveillance.
KEYWORDS:
antigenicity, hemagglutinin, influenza
PMID:
24531414
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24531414