Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes
Extensive variation in the IAV HA globular domain severely impedes influenza vaccination. Recent findings demonstrate that StRAbs, specific Abs to the highly conserved stem region of HA, can protect hosts against a broad variety of influenza virus strains. In investigating the binding of StRAbs to HA during its biogenesis in IAV-infected cells, we find that these Abs can bind HA monomers prior to their trimerization in the GC. Binding to HA becomes temperature-dependent, however, as N-linked oligosaccharides mature during transport of trimerized HA through the GC to the cell surface. Our findings support the potential use of monomeric HA stem immunogens to induce broadly neutralizing Abs, but raise the possibility of eventual viral escape from StRAbs, based on structural alterations in the HA that increase steric hindrance of HA stem N-linked glycans on StRAb binding.
Vyšlo v časopise:
Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004204
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004204
Souhrn
Extensive variation in the IAV HA globular domain severely impedes influenza vaccination. Recent findings demonstrate that StRAbs, specific Abs to the highly conserved stem region of HA, can protect hosts against a broad variety of influenza virus strains. In investigating the binding of StRAbs to HA during its biogenesis in IAV-infected cells, we find that these Abs can bind HA monomers prior to their trimerization in the GC. Binding to HA becomes temperature-dependent, however, as N-linked oligosaccharides mature during transport of trimerized HA through the GC to the cell surface. Our findings support the potential use of monomeric HA stem immunogens to induce broadly neutralizing Abs, but raise the possibility of eventual viral escape from StRAbs, based on structural alterations in the HA that increase steric hindrance of HA stem N-linked glycans on StRAb binding.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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