Fucose Binding Cancels out Mechanical Differences between Distinct Human Noroviruses

Abstract

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.

Collision induced unfolding and molecular dynamics simulations of norovirus capsid dimers reveal strain-specific stability profiles

“…7,9 A higher instability of the critical N-terminus may also influence the overall decreased stability of the Norwalk capsid compared to Kawasaki as shown in other studies. 7,10,12 In light of the new data presented here together with earlier results, the VP1 dimer is becoming the likely origin of the strain-dependent distinction in physical properties of the fully assembled capsids. To our knowledge, we present here the first study of combining both experimental and theoretical research on the unfolding of norovirus dimers, providing valuable insights into their stability and details about their behaviour and thus adding to the compounding evidence on previously identified structural linchpins.…”

“…Atomic force microscopy unveiled differences in the elasticity of the capsids, also demonstrating Kawasaki to be more stable than Norwalk. 10 A caveat here is of course the difference from gas phase, where we test unfolding, and in-solution testing. In the gas phase, hydrophobic contacts are weakened and hydrophilic ones are strengthened.…”

“…3 Noroviruses are the leading cause of viral gastroenteritis, 4,5 an acute inflammation of the gastrointestinal tract that can cause severe complications particularly for infants, the elderly or people with compromised immune systems. 6 The norovirus capsid has been subject to several studies on the aforementioned assembly and stability, 7–10 as they are an essential part of understanding viral mechanisms of infection. 11 This is especially true for a foodborne pathogen that has demonstrated extraordinary environmental stability.…”

Overview of the 2023 Physical Virology Gordon Research Conference—Viruses at Multiple Levels of Complexity

“…In more fundamental sciences, viruses are ideal model systems for studying mechanisms underlying self-assembly, genome packaging and release, allostery, membrane dynamics, and the efficient passage of nanoscale particles through membranes. The COVID-19 pandemic has highlighted the need for these cross-disciplinary approaches to understand viral biology [ 15 , 16 , 17 ], predict their global spread and impact, and develop new treatments. In addition to advancing antiviral strategies and cell biology, the knowledge acquired from these studies and the viral particles themselves are enabling researchers to engineer virus-based platforms for biomedical and nanomaterial applications, such as gene delivery or optoelectronics.…”