Wasik Brian R, Barnard Karen N, Ossiboff Robert J, Khedri Zahra, Feng Kurtis H, Yu Hai, Chen Xi, Perez Daniel R, Varki Ajit, Parrish Colin R
Department of Microbiology and Immunology, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
mSphere. 2017 Sep 6;2(5). doi: 10.1128/mSphere.00379-16. eCollection 2017 Sep-Oct.
Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins. However, the distribution of modified Sia forms and their effects on pathogen-host interactions are still poorly understood. Here we used probes developed from viral Sia-binding proteins to detect O-acetylated (4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl) Sias displayed on the tissues of some natural or experimental hosts for influenza viruses. These modified Sias showed highly variable displays between the hosts and tissues examined. The 9-O-acetyl (and 7,9-) modified Sia forms were found on cells and tissues of many hosts, including mice, humans, ferrets, guinea pigs, pigs, horses, dogs, as well as in those of ducks and embryonated chicken egg tissues and membranes, although in variable amounts. The 4-O-acetyl Sias were found in the respiratory tissues of fewer animals, being primarily displayed in the horse and guinea pig, but were not detected in humans or pigs. The results suggest that these Sia variants may influence virus tropisms by altering and selecting their cell interactions. Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses.
唾液酸（Sias）是许多不同动物的细胞和组织上展示的重要聚糖，并且是包括流感病毒在内的病原体结合和修饰的常见靶点。流感病毒血凝素在感染其正常宿主期间结合唾液酸，而编码的神经氨酸酶和/或酯酶去除或修饰唾液酸以允许病毒粒子释放或防止重新结合。唾液酸以多种修饰形式天然存在，修饰的唾液酸可通过改变与病毒糖蛋白的相互作用来改变流感病毒的宿主嗜性。然而，修饰的唾液酸形式的分布及其对病原体-宿主相互作用的影响仍知之甚少。在这里，我们使用从病毒唾液酸结合蛋白开发的探针来检测在一些流感病毒天然或实验宿主组织上展示的O-乙酰化（4-O-乙酰基、9-O-乙酰基和7,9-O-乙酰基）唾液酸。这些修饰的唾液酸在检查的宿主和组织之间显示出高度可变的表现。发现9-O-乙酰基（和7,9-）修饰的唾液酸形式存在于许多宿主的细胞和组织中，包括小鼠、人类、雪貂、豚鼠、猪、马、狗，以及鸭和鸡胚组织及膜中，尽管数量各不相同。4-O-乙酰基唾液酸在较少动物的呼吸道组织中被发现，主要存在于马和豚鼠中，但在人类或猪中未检测到。结果表明，这些唾液酸变体可能通过改变和选择它们与细胞的相互作用来影响病毒嗜性。唾液酸（Sias）是控制或调节许多正常细胞和组织功能同时还与包括许多不同病毒在内的多种病原体相互作用的关键聚糖。唾液酸以多种不同形式天然展示，在几个位置有修饰，这可以改变它们与病原体的功能相互作用。此外，唾液酸经常被宿主或病原体酯酶或唾液酸酶（神经氨酸酶）等酶修饰或去除，唾液酸修饰可以改变这些酶活性以影响病原体感染。不同宿主和组织中唾液酸的化学多样性可能会改变病原体-宿主相互作用并影响感染结果。在这里，我们探索了4-O-乙酰基、9-O-乙酰基和7,9-O-乙酰基修饰的唾液酸形式在小鼠、人类、鸟类、豚鼠、雪貂、猪、马和狗等流感病毒感染的一些靶组织中的展示情况，这些动物涵盖了这些病毒的许多天然和实验室宿主。
