Structural Basis for Human Norovirus Capsid Binding to Bile Acids

• DOI: 10.1128/jvi.01581-18
• Publication Date: 2018-10-22T10:22:16Z
• Authors: Turgay Kilic; Anna Koromyslova; Grant S. Hansman
• Keywords: Infectivity

A recently developed human norovirus cell culture system revealed that the presence of bile enhanced or was an essential requirement for growth certain genotypes. Before this discovery, histo-blood group antigens (HBGAs) were only well-studied cofactor known noroviruses, and there evidence several genotypes poorly bound HBGAs. Therefore, purpose study to investigate how capsids interact with acids. We found acids had low-micromolar affinities GII.1, GII.10, GII.19 but did not bind GI.1, GII.3, GII.4, GII.17. showed acid at a partially conserved pocket on capsid-protruding (P) domain using X-ray crystallography. Amino sequence alignment structural analysis delivered explanation selective binding. Intriguingly, we discovered binding critical step stabilize P loops optimally placed amino side chain (Asp375) HBGAs in otherwise HBGA nonbinder (GII.1). Furthermore, binder (GII.10). Altogether, these new data suggest functions as loop-stabilizing regulator enhancer genotypes.IMPORTANCE Given virions likely during natural infection, our (GII.1) can be converted after is major significance. Our provide direct that, like HBGAs, interaction capsid important However, more unanswered questions seem arise from discoveries. For example, association between prevalence genotypes? That is, GII.1 GII.10 (bile binders) rarely caused outbreaks, whereas GII.4 GII.17 nonbinders) responsible large epidemics. it seems plausible require acids, others have modified their requirements capsid.