Serveur d'exploration sur la grippe en Espagne

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Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin.

Identifieur interne : 000231 ( Main/Exploration ); précédent : 000230; suivant : 000232

Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin.

Auteurs : Blanca García-Barreno [Espagne] ; Teresa Delgado [Espagne] ; Sonia Benito [Espagne] ; Inmaculada Casas [Espagne] ; Francisco Pozo [Espagne] ; María Teresa Cuevas [Espagne] ; Vicente Mas [Espagne] ; Alfonsina Trento [Espagne] ; Ariel Rodriguez-Frandsen [Espagne] ; Ana Falc N [Espagne] ; Juan Ortín [Espagne] ; Amelia Nieto [Espagne] ; José A. Melero [Espagne]

Source :

RBID : pubmed:24531414

Descripteurs français

English descriptors

Abstract

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.

DOI: 10.1099/vir.0.061598-0
PubMed: 24531414


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Le document en format XML

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<name sortKey="Rodriguez Frandsen, Ariel" sort="Rodriguez Frandsen, Ariel" uniqKey="Rodriguez Frandsen A" first="Ariel" last="Rodriguez-Frandsen">Ariel Rodriguez-Frandsen</name>
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<name sortKey="Ortin, Juan" sort="Ortin, Juan" uniqKey="Ortin J" first="Juan" last="Ortín">Juan Ortín</name>
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<name sortKey="Melero, Jose A" sort="Melero, Jose A" uniqKey="Melero J" first="José A" last="Melero">José A. Melero</name>
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<name sortKey="Delgado, Teresa" sort="Delgado, Teresa" uniqKey="Delgado T" first="Teresa" last="Delgado">Teresa Delgado</name>
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<name sortKey="Pozo, Francisco" sort="Pozo, Francisco" uniqKey="Pozo F" first="Francisco" last="Pozo">Francisco Pozo</name>
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<name sortKey="Cuevas, Maria Teresa" sort="Cuevas, Maria Teresa" uniqKey="Cuevas M" first="María Teresa" last="Cuevas">María Teresa Cuevas</name>
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<term>Mutant Proteins (immunology)</term>
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<term>Antigènes viraux (immunologie)</term>
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<div type="abstract" xml:lang="en">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. </div>
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<Year>2014</Year>
<Month>06</Month>
<Day>10</Day>
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<Month>02</Month>
<Day>26</Day>
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<AbstractText>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. </AbstractText>
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<li>Espagne</li>
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<name sortKey="Rodriguez Frandsen, Ariel" sort="Rodriguez Frandsen, Ariel" uniqKey="Rodriguez Frandsen A" first="Ariel" last="Rodriguez-Frandsen">Ariel Rodriguez-Frandsen</name>
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</record>

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   |texte=   Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin.
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