Moleculaire Biofysica, Zernike Instituut, Rijksuniversiteit Groningen, 9747AG Groningen, The Netherlands.
CSSB Centre for Structural Systems Biology, Deutsches Elektronen-Synchrotron (DESY) & Leibniz Institute of Virology (LIV), 22607 Hamburg, Germany.
Viruses. 2023 Jun 30;15(7):1482. doi: 10.3390/v15071482.
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.
大多数人类和家畜的非细菌性胃肠炎是由诺如病毒引起的。与大多数 RNA 病毒一样，频繁的突变导致了各种诺如病毒变体。诺如病毒对岩藻糖的依赖性结合模式被认为有助于诺如病毒感染。然而，尚不清楚依赖于菌株的功能背后的分子机制是什么。在这项研究中，我们通过应用原子力显微镜（AFM）纳米压痕技术研究了三种不同的人类诺如病毒变体的类诺如病毒样颗粒（noroVLPs）。我们发现，即使是来自同一基因群的诺如病毒变体，其病毒机械性能也存在差异。然后对 noroVLPs 进行岩藻糖处理。令人惊讶的是，岩藻糖处理后，先前在这些变体之间发现的病毒机械性能的显著差异减少了。我们将诺如病毒 P 结构域在结合岩藻糖时的动态切换归因于测试的诺如病毒变体之间病毒机械性能差异的减小。这些发现揭示了诺如病毒衣壳用于适应环境变化并可能增加细胞感染的机制。由此，朝着将病毒机械性能与病毒流行联系起来迈出了新的一步。
