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

• Published in: Virology (New York, N.Y.) N.Y.), 2015-12, Vol.486, p.134-145
• Main Authors: Hervé, Pierre-Louis, Lorin, Valérie, Jouvion, Grégory, Da Costa, Bruno, Escriou, Nicolas
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigenic drift; Epitope Mapping; Female; Glycosylation; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Hemagglutinin H5; Highly pathogenic Influenza A H5N1; Humans; Infectious Disease; Influenza A Virus, H3N2 Subtype - chemistry; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H3N2 Subtype - metabolism; Influenza A Virus, H5N1 Subtype - chemistry; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - immunology; Influenza A Virus, H5N1 Subtype - metabolism; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - virology; Life Sciences; Mice; Mice, Inbred BALB C; N-glycosylation; Neutralization Tests; Neutralizing antibodies
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2015.08.033

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.