Asymptomatic infections with polyomaviruses in humans are common, but these small viruses can cause severe diseases in immunocompromised hosts. New Jersey polyomavirus (NJPyV) was identified via a muscle biopsy in an organ transplant recipient with systemic vasculitis, myositis, and retinal blindness, and human polyomavirus 12 (HPyV12) was detected in human liver tissue. The evolutionary origins and potential diseases are not well understood for either virus. In order to define their receptor engagement strategies, we first used nuclear magnetic resonance (NMR) spectroscopy to establish that the major capsid proteins (VP1) of both viruses bind to sialic acid in solution. We then solved crystal structures of NJPyV and HPyV12 VP1 alone and in complex with sialylated glycans. NJPyV employs a novel binding site for a α2,3-linked sialic acid, whereas HPyV12 engages terminal α2,3- or α2,6-linked sialic acids in an exposed site similar to that found in Trichodysplasia spinulosa-associated polyomavirus (TSPyV). Gangliosides or glycoproteins, featuring in mammals usually terminal sialic acids, are therefore receptor candidates for both viruses. Structural analyses show that the sialic acid-binding site of NJPyV is conserved in chimpanzee polyomavirus (ChPyV) and that the sialic acid-binding site of HPyV12 is widely used across the entire polyomavirus family, including mammalian and avian polyomaviruses. A comparison with other polyomavirus-receptor complex structures shows that their capsids have evolved to generate several physically distinct virus-specific receptor-binding sites that can all specifically engage sialylated glycans through a limited number of contacts. Small changes in each site may have enabled host-switching events during the evolution of polyomaviruses.

中文翻译：

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多瘤病毒家族中聚糖受体特异性的结构基础和进化。

在人类中，多瘤病毒无症状感染是很常见的，但是这些小病毒可以在免疫受损的宿主中引起严重的疾病。通过肌肉活检在患有系统性血管炎，肌炎和视网膜盲的器官移植受者中鉴定出新泽西州多瘤病毒（NJPyV），并在人肝组织中检测到人多瘤病毒12（HPyV12）。对于这两种病毒，其进化起源和潜在疾病均知之甚少。为了定义它们的受体参与策略，我们首先使用核磁共振（NMR）光谱来确定两种病毒的主要衣壳蛋白（VP1）与溶液中的唾液酸结合。然后，我们单独和与唾液酸化聚糖复合解决了NJPyV和HPyV12 VP1的晶体结构。NJPyV对α2,3-连接的唾液酸采用了新的结合位点，棘状增生相关多瘤病毒（TSPyV）。因此，在哺乳动物中通常以末端唾液酸为特征的神经节苷脂或糖蛋白是两种病毒的候选受体。结构分析表明，NJPyV的唾液酸结合位点在黑猩猩多瘤病毒（ChPyV）中是保守的，HPyV12的唾液酸结合位点已在整个多瘤病毒家族中广泛使用，包括哺乳动物和禽类多瘤病毒。与其他多瘤病毒-受体复合物结构的比较表明，它们的衣壳已经进化为产生几个物理上不同的病毒特异性受体结合位点，这些位点都可以通过有限数量的接触特异性地与唾液酸化的聚糖结合。在多瘤病毒的进化过程中，每个站点的微小变化都可能启用了主机切换事件。