A single amino acid in the viral capsid makes a major contribution to the interaction between human norovirus GII.6 and the bacterial Psl exopolysaccharide

Human noroviruses are a leading cause of foodborne gastroenteritis worldwide, and oysters are a major vector for their transmission. Previous work has shown that the Psl exopolysaccharide (EPS) from oyster-derived Pseudomonas composti strain ODT-54 binds to human norovirus GII.6, but the molecular mechanism remains unknown. Here, we combined molecular docking, dynamics simulations, Molecular Mechanics Poisson-Boltzmann Surface Area calculations, and site-directed mutagenesis to investigate this interaction. Our results suggest that the composition and conformation of the B loop contribute importantly to EPS-mediated bioaccumulation, and that residue valine 297 (V297) in the B loop of the GII.6 ( KX752057.1 ) P domain is an important determinant of Psl binding. Our findings provide residue-level evidence that the composition and conformation of the B loop, particularly residue V297, contributes to the interaction between human norovirus GII.6 and the bacterial Psl exopolysaccharide.

IMPORTANCE

The persistence of human noroviruses in environmental and food matrices can be facilitated by their interaction with bacterial surface components, such as exopolysaccharides (EPS). However, the molecular basis of norovirus-bacteria interactions remains poorly understood. In this study, we demonstrate that the GII.6 norovirus capsid protein specifically binds to the Pseudomonas-derived Psl EPS via a key residue, valine 297, located in the hypervariable B loop of the P2 subdomain. This interaction is genotype-specific, with GII.6 exhibiting significantly stronger binding than the epidemic GII.4 strain. Our findings reveal a previously unrecognized mechanism of viral environmental persistence mediated by bacterial EPS and highlight the role of capsid loop flexibility and residue-level variation in shaping norovirus-host-environment interactions. This work provides a structural and dynamic framework for understanding norovirus ecology and may inform future strategies for mitigating viral contamination in food and water systems.