The shape of escape: decoding the structural effects and evolutionary trajectories involving N-glycosylation in influenza a hemagglutinin
Active Project Grant Awarded Last action
- Award ID
- F31AI200275
- Recipient
-
ST. Jude Children's Research Hospital Graduate School Of Biomedical Sciences, LLC UEI MN2LFZNE4HH3
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $49,114
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Place of performance
- Memphis, TN 38105, USA
Award details come from USAspending.gov.
Description
- Abstract
- Influenza a virus (IAV) remains a formidable threat to global health due to its high mutation rate and capacity for immune evasion, which challenge the effectiveness of seasonal vaccines and limit our ability to anticipate emerging strains. A major contributor to this immune escape is N-glycosylation site emergence (NSE) on hemagglutinin (HA), which can shield key regions from the host immune response. However, we currently lack a predictive framework to forecast when, where, and why these glycosylation events arise. This proposed work addresses that critical knowledge GAP by integrating codon-level mutational probabilities, structural modeling, and molecular dynamics simulations to uncover the genetic and biophysical rules governing NSE emergence and their impact on viral evolution. In aim 1, I will analyze HA sequences from H1N1 and H3N2 strains to define the common route by which mutations give rise to nses and assess their structural positioning and immune relevance. I will utilize established methods to determine IAV strain NSE genotype accessibility and trace the mutational trajectories that give rise to NSE motifs. Additionally, I will evaluate the structural positioning and epitope coverage of rare, common, and hypothetical glycosylation events using predicted, glycosylated HA structures. In aim 2, I will perform molecular dynamics simulations of key historical NSE events in human-circulating H1N1 and H3N2 IAV populations to evaluate how N-glycan shielding alters HA surface accessibility and reshapes local evolutionary trajectories. These simulations will illuminate how glycans influence residue conservation, epitope exposure, and future mutational potential. Together, these aims will pave the groundwork for a rigorous, mechanistic method for forecasting immune escape in IAV, enhancing our ability to identify high-risk strains in real time and informing vaccine strain selection. The proposed work leverages cutting-edge computational tools and a novel evolutionary lens to address a longstanding challenge in influenza biology, with broad implications for anticipating viral adaptation in other rapidly evolving pathogens.
Quick answers
Who received award F31AI200275?
F31AI200275 was awarded to ST. Jude Children's Research Hospital Graduate School Of Biomedical Sciences, LLC by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on December 4, 2026.
How much is award F31AI200275 worth?
$49,114 has been obligated on F31AI200275.
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