PDF(Pubmed)
Abstract：
The surfaces of cells and enveloped viruses alike are coated in carbohydrates that play multifarious roles in infection and immunity. Organisms across all kingdoms of life make use of a diverse set of monosaccharide subunits, glycosidic linkages, and branching patterns to encode information within glycans. Accordingly, sugar-patterning enzymes and glycan binding proteins play integral roles in cell and organismal biology, ranging from glycoprotein quality control within the endoplasmic reticulum to lymphocyte migration, coagulation, inflammation, and tissue homeostasis. Unsurprisingly, genes involved in generating and recognizing oligosaccharide patterns are playgrounds for evolutionary conflicts that abound in cross-species interactions, exemplified by the myriad plant lectins that function as toxins. In vertebrates, glycans bearing acidic nine-carbon sugars called sialic acids are key regulators of immune responses. Various bacterial and fungal pathogens adorn their cells in sialic acids that either mimic their hosts\' or are stolen from them. Yet, how viruses commandeer host sugar-patterning enzymes to thwart immune responses remains poorly studied. Here, we review examples of viruses that interact with sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immune cell receptors that regulate toll-like receptor signaling and govern glycoimmune checkpoints, while highlighting knowledge gaps that merit investigation. Efforts to illuminate how viruses leverage glycan-dependent checkpoints may translate into new clinical treatments that uncloak viral antigens and infected cell surfaces by removing or masking immunosuppressive sialoglycans, or by inhibiting viral gene products that induce their biosynthesis. Such approaches may hold the potential to unleash the immune system to clear long intractable chronic viral infections.
摘要：
细胞和包膜病毒的表面都涂有碳水化合物，这些碳水化合物在感染和免疫中起着多种作用。所有生命王国的生物体都利用了各种各样的单糖亚基，糖苷键，和分支模式来编码聚糖内的信息。因此，糖模式酶和聚糖结合蛋白在细胞和生物体生物学中起着不可或缺的作用，从内质网内的糖蛋白质量控制到淋巴细胞迁移，凝血,炎症,和组织稳态。毫不奇怪,参与产生和识别寡糖模式的基因是进化冲突的场所，这些冲突在跨物种相互作用中比比皆是，以作为毒素的无数植物凝集素为例。在脊椎动物中，带有酸性九碳糖的聚糖称为唾液酸是免疫反应的关键调节剂。各种细菌和真菌病原体在唾液酸中装饰它们的细胞，这些唾液酸要么模仿它们的宿主，要么从它们那里被偷走。然而，病毒如何命令宿主糖模式酶来阻止免疫反应的研究还很少。这里,我们回顾了与唾液酸结合免疫球蛋白样凝集素（Siglecs）相互作用的病毒的例子，一个调节toll样受体信号并控制糖免疫检查点的免疫细胞受体家族，同时突出了值得调查的知识差距。阐明病毒如何利用聚糖依赖的检查点的努力可能会转化为新的临床治疗方法，通过去除或掩盖免疫抑制的唾液酸聚糖来掩盖病毒抗原和受感染的细胞表面，或通过抑制诱导其生物合成的病毒基因产物。这种方法可能具有释放免疫系统以清除长期棘手的慢性病毒感染的潜力。
