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oai:repisalud.isciii.es:20.500.12105/154802025-04-30T06:21:50Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Garcia-Barreno, Blanca author Delgado-Romero, Teresa author Benito, Sonia author Casas Flecha, Inmaculada author Pozo Sanchez, Francisco author Cuevas, Maria Teresa author Mas-Lloret, Vicente author Trento, Alfonsina author Rodriguez-Frandsen, Ariel author Falcon, Ana author Ortin, Juan author Nieto, Amelia author Melero, Jose Antonio author 2014-05 Murine hybridomas producing neutralizing mAbs specific to the pandemic influenza virus A/California/07/2009 haemagglutinin (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/Extremadura/RR6530/2010) lacked reactivity with the mAbs and carried two unique mutations in the HA head (S88Y and K136N) that were required simultaneously to eliminate reactivity with the murine antibodies. This unusual requirement directly illustrates the phenomenon of enhanced antigenic change proposed previously for the accumulation of simultaneous amino acid substitutions at antigenic sites of the influenza A virus HA during virus evolution (Shih et al., Proc Natl Acad Sci USA, 104 , 6283-6288, 2007). The changes found in the A/Extremadura/RR6530/2010 HA were not found in escape mutants selected in vitro with one of the mAbs, which contained instead nearby single amino acid changes in the HA head. Thus, either single or double point mutations may similarly alter epitopes of the new antigenic site identified in this work in the 2009 H1N1 pandemic virus HA. Moreover, this site is relevant for the human antibody response, as shown by competition of mAbs and human post-infection 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. J Gen Virol. 2014 May;95(Pt 5):1033-1042. 10.1099/vir.0.061598-0 1465-2099 The Journal of general virology 24531414 http://hdl.handle.net/20.500.12105/15480 Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin