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Virology. 2015 Dec;486:134-45. doi: 10.1016/j.virol.2015.08.033. Epub 2015 Oct 1.

Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin induces the escape of highly pathogenic avian influenza A H5N1 viruses from vaccine-induced immunity.

Author information

1
Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, 25-28 rue du Docteur Roux, F-75015 Paris, France; CNRS UMR 3569, 25-28 rue du Docteur Roux, F-75015 Paris, France; Université Paris Diderot, Sorbonne, Paris Cité, EA 302, 25-28 rue du Docteur Roux, Paris, France. Electronic address: plherve@jouy.inra.fr.
2
Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, 25-28 rue du Docteur Roux, F-75015 Paris, France; CNRS UMR 3569, 25-28 rue du Docteur Roux, F-75015 Paris, France; Université Paris Diderot, Sorbonne, Paris Cité, EA 302, 25-28 rue du Docteur Roux, Paris, France.
3
Institut Pasteur, Unité d'histopathologie Humaine et Modèles Animaux, 25-28 rue du Docteur Roux, F-75015 Paris, France.
4
Institut National de la Recherche Agronomique (INRA), Molecular Virology and Immunology unit (VIM), UR892, Domaine de Vilvert, F-78350 Jouy-en-Josas, France.
5
Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, 25-28 rue du Docteur Roux, F-75015 Paris, France; CNRS UMR 3569, 25-28 rue du Docteur Roux, F-75015 Paris, France; Université Paris Diderot, Sorbonne, Paris Cité, EA 302, 25-28 rue du Docteur Roux, Paris, France. Electronic address: nicolas.escriou@pasteur.fr.

Abstract

Highly pathogenic avian influenza A H5N1 viruses remain endemic in poultry in several countries and still constitute a pandemic threat. Since the early 20th century, we experienced four influenza A pandemics. H3N2 and H1N1pdm09 viruses that respectively emerged during 1968 and 2009 pandemics are still responsible for seasonal epidemics. These viruses evolve regularly by substitutions in antigenic sites of the hemagglutinin (HA), which prevent neutralization by antibodies directed against previous strains (antigenic drift). For seasonal H3N2 viruses, an addition of N-glycosylation sites (glycosites) on H3 contributed to this drift. Here, we questioned whether additional glycosites on H5 could induce an escape of H5N1 virus from neutralization, as it was observed for seasonal H3N2 viruses. Seven H5N1 mutants were produced by adding glycosites on H5. The most glycosylated virus escaped from neutralizing antibodies, in vitro and in vivo. Furthermore, a single additional glycosite was responsible for this escape.

KEYWORDS:

Antigenic drift; Hemagglutinin H5; Highly pathogenic Influenza A H5N1; N-glycosylation; Neutralizing antibodies

PMID:
26433051
DOI:
10.1016/j.virol.2015.08.033
[Indexed for MEDLINE]
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