title: 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.
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.
authors.affiliation: 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.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Hervé
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lorin
authors.affiliation: Institut Pasteur, Unité d'histopathologie Humaine et Modèles Animaux, 25-28 rue du Docteur Roux, F-75015 Paris, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Jouvion
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Molecular Virology and Immunology unit (VIM), UR892, Domaine de Vilvert, F-78350 Jouy-en-Josas, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Da Costa
authors.affiliation: 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Escriou
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D018604:Epitope Mapping; D005260:Female; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C109963:hemagglutinin, avian influenza A virus
keywords: Antigenic drift; Hemagglutinin H5; Highly pathogenic Influenza A H5N1; N-glycosylation; Neutralizing antibodies