Fucose Binding Cancels out Mechanical Differences between Distinct Human Noroviruses

The majority of nonbacterial gastroenteritis in humans and livestock is caused by noroviruses.
Like most RNA viruses, frequent mutations result in various norovirus variants. The strain-dependent
binding profiles of noroviruses to fucose are supposed to facilitate norovirus infection. It remains unclear, however, what the molecular mechanism behind strain-dependent functioning is. In this study,
by applying atomic force microscopy (AFM) nanoindentation technology, we studied norovirus-like
particles (noroVLPs) of three distinct human norovirus variants. We found differences in viral mechanical properties even between the norovirus variants from the same genogroup. The noroVLPs
were then subjected to fucose treatment. Surprisingly, after fucose treatment, the previously found
considerable differences in viral mechanical properties among these variants were diminished. We
attribute a dynamic switch of the norovirus P domain upon fucose binding to the reduced differences
in viral mechanical properties across the tested norovirus variants. These findings shed light on the
mechanisms used by norovirus capsids to adapt to environmental changes and, possibly, increase
cell infection. Hereby, a new step towards connecting viral mechanical properties to viral prevalence
is taken.