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首页> 外文期刊>Emerging microbes & infections. >Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses
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Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses

机译：GII猪诺如病毒与其密切相关的GII人诺如病毒的宿主配体特异性变化的结构基础

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Diverse noroviruses infect humans and animals via the recognition of host-specific glycan ligands. Genogroup II (GII) noroviruses consist of human noroviruses (huNoVs) that generally bind histo-blood group antigens (HBGAs) as host factors and three porcine norovirus (porNoV) genotypes (GII.11/18/19) that form a genetic lineage lacking HBGA-binding ability. Thus, these GII porNoVs provide an excellent model to study norovirus evolution with host ligand specificity changes. Here we solved the crystal structures of a native GII.11 porNoV P protein and a closely-related GII.3 huNoV P protein complexed with an HBGA, focusing on the HBGA-binding sites (HBSs) compared with the previously known ones to understand the structural basis of the host ligand specificity change. We found that the GII.3 huNoV binds HBGAs via a conventional GII HBS that uses an arginine instead of the conserved aromatic residue for the required Van der Waals interaction, while the GII.11 porNoV HBS loses its HBGA-binding function because of two mutations (Q355/V451). A mutant that reversed the two mutated residues back to the conventional A355/Y451 restored the HBGA-binding function of the GII.11 porNoV P protein, which validated our observations. Similar mutations are also found in GII.19 porNoVs and a GII.19 P protein mutant with double reverse mutations restored the HBS function. This is the first reconstruction of a functional HBS based on one with new host specificity back to its parental one. These data shed light on the molecular basis of structural adaptation of the GII porNoVs to the pig hosts through mutations at their HBSs.
机译：多种诺如病毒通过识别宿主特异性聚糖配体感染人类和动物。 Genogroup II（GII）诺如病毒由通常结合组织血型组抗原（HBGA）作为宿主因子的人类诺如病毒（huNoV）和三种猪诺如病毒（porNoV）基因型（GII.11 / 18/19）组成，这些基因缺乏HBGA结合能力。因此，这些GII porNoV为研究诺如病毒随着宿主配体特异性变化而进化提供了一个极好的模型。在这里，我们解决了天然GII.11 porNoV P蛋白和与HBGA复合的密切相关的GII.3 huNoV P蛋白的晶体结构，重点是与以前已知的HBGA结合位点（HBS）相比，以了解宿主配体特异性改变的结构基础。我们发现，GII.3 huNoV通过常规的GII HBS通过必需的范德华相互作用使用精氨酸代替保守的芳族残基来结合HBGA，而GII.11 porNoV HBS由于两个突变而失去了HBGA结合功能。 （Q355 / V451）。将两个突变残基逆转回常规A355 / Y451的突变体恢复了GII.11 porNoV P蛋白的HBGA结合功能，这验证了我们的观察结果。在GII.19 porNoV中也发现了类似的突变，具有双重反向突变的GII.19 P蛋白突变恢复了HBS功能。这是基于功能性HBS的首次重构，该功能基于具有新的宿主特异性的HBS（回到其亲本）。这些数据揭示了GII porNoV通过其HBS突变而适应猪宿主的分子基础。

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