Norovirus devours human milk oligosaccharides rich in α-fucose

Abstract

Human norovirus binding to histo-blood group antigens (HBGAs) is thought to direct their entry into host cells. However, the glycan epitopes characteristic of HBGAs are also present on oligosaccharides abundant in human milk. In this issue of JBC, Hanisch et al compared norovirus binding to human gastric mucins and human milk oligosaccharides, finding those bound most avidly are rich in α-fucose. Mimicry of these epitopes with α-fucose multivalently displayed on other carbohydrate scaffolds successfully scavenged this prevalent virus, providing new insights into norovirus biology and clues for future therapeutic development.

Figure 1.

Oligosaccharide epitopes and their viral partner. A, humans infected by the prevalent norovirus GII.4 strain have an active FUT2 enzyme that transfers fucose to form the H-type 1 blood group antigen and perhaps the FUT3 enzyme that forms the Le-b antigen. Yellow circle, galactose; blue square, GlcNAc; red triangle, fucose. Fucoidan, from Fucus vesiculosus, contains α-fucoside branches that serve as a structural decoy for norovirus binding. B, the Norwalk virus capsid has icosahedral symmetry (green lines, in Protein Data Bank entry 1IHM (4)) displaying 180 copies of the major viral protein (3). The HBGA-binding P2 subdomain is a small β-barrel (white) that can be seen emanating from the protruding P domain surface.