title: Fitness costs limit influenza A virus hemagglutinin glycosylation as an immune evasion strategy.
abstract: Here, we address the question of why the influenza A virus hemagglutinin (HA) does not escape immunity by hyperglycosylation. Uniquely among dozens of monoclonal antibodies specific for A/Puerto Rico/8/34, escape from H28-A2 neutralization requires substitutions introducing N-linked glycosylation at residue 131 or 144 in the globular domain. This escape decreases viral binding to cellular receptors, which must be compensated for by additional substitutions in HA or neuraminidase that enable viral replication. Sequence analysis of circulating H1 influenza viruses confirms the in vivo relevance of our findings: natural occurrence of glycosylation at residue 131 is always accompanied by a compensatory mutation known to increase HA receptor avidity. In vaccinated mice challenged with WT vs. H28-A2 escape mutants, the selective advantage conferred by glycan-mediated global reduction in antigenicity is trumped by the costs of diminished receptor avidity. These findings show that, although N-linked glycosylation can broadly diminish HA antigenicity, fitness costs restrict its deployment in immune evasion.
authors: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Suman R
authors: SR
authors: Das
authors: Scott E
authors: SE
authors: Hensley
authors: Alexandre
authors: A
authors: David
authors: Loren
authors: L
authors: Schmidt
authors: James S
authors: JS
authors: Gibbs
authors: Pere
authors: P
authors: Puigbò
authors: William L
authors: WL
authors: Ince
authors: Jack R
authors: JR
authors: Bennink
authors: Jonathan W
authors: JW
authors: Yewdell
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D004285:Dogs; D018604:Epitope Mapping; D006031:Glycosylation; D006388:Hemagglutinins / Q000737:chemistry*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D009980:Influenza A virus / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D014779:Virus Replication
chemical_list: D000941:Antigens; D006388:Hemagglutinins