Sialic acids (Sia) are the primary receptors for influenza viruses and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C-4, C-7, C-8, and C-9 positions and N-acetyl or N-glycolyl at C-5. They can also vary in their linkages, including α2-3 or α2-6 linkages. Here, we analyze the distribution of modified Sia in cells and tissues of wild-type mice or in mice lacking CMP-N-acetylneuraminic acid hydroxylase (CMAH) enzyme, which synthesizes N-glycolyl (Neu5Gc) modifications. We also examined the variation of Sia forms on erythrocytes and in saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal (GI) tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a high degree of variability in display of modified Sia between different species. IAV HAs from different virus strains showed consistently reduced binding to both Neu5Gc- and O-acetyl-modified Sia; however, while IAV NAs were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV and may affect both pathogens and the normal flora of different mucosal sites.IMPORTANCE Sialic acids (Sia) are involved in numerous different cellular functions and are receptors for many pathogens. Sia come in chemically modified forms, but we lack a clear understanding of how they alter interactions with microbes. Here, we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably among different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.

中文翻译：

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粘液和红细胞上的修饰唾液酸可抑制甲型流感病毒血凝素和神经氨酸酶功能。


唾液酸（Sia）是流感病毒的主要受体，广泛存在于细胞表面和分泌的粘液中。 Sia可以以变体形式存在，包括在C-4、C-7、C-8和C-9位置处的O-乙酰基修饰以及在C-5处的N-乙酰基或N-乙醇酰基修饰。它们的连接也可以不同，包括 α2-3 或 α2-6 连接。在这里，我们分析了修饰的 Sia 在野生型小鼠或缺乏 CMP-N-乙酰神经氨酸羟化酶 (CMAH) 酶的小鼠的细胞和组织中的分布，该酶合成 N-乙醇酰 (Neu5Gc) 修饰。我们还检查了不同动物的红细胞和唾液中 Sia 形式的变化。为了确定 Sia 修饰对甲型流感病毒 (IAV) 感染的影响，我们测试了对血凝素 (HA) 结合和神经氨酸酶 (NA) 裂解的影响。我们证实，9-O-乙酰基、7,9-O-乙酰基、4-O-乙酰基和 Neu5Gc 修饰在小鼠组织中广泛但差异性表达，在呼吸道和胃肠道 (GI) 中检测到最高水平。唾液中分泌的粘蛋白和红细胞表面蛋白在不同物种之间显示修饰的 Sia 的表现出高度的变异性。来自不同病毒株的 IAV HA 与 Neu5Gc 和 O-乙酰基修饰的 Sia 的结合持续减少；然而，虽然 IAV NA 受到 Neu5Gc 和 O-乙酰基修饰的抑制，但 NA 类型之间存在显着差异。因此，粘液中 Sia 的修饰可能对 IAV 的功能产生强有力的影响，并可能影响病原体和不同粘膜部位的正常菌群。 重要性 唾液酸 (Sia) 参与许多不同的细胞功能，并且是许多病原体的受体。 Sia 以化学修饰形式出现，但我们对它们如何改变与微生物的相互作用缺乏清晰的了解。在这里，我们检查了修饰的 Sia 在小鼠组织、唾液中分泌的粘液和红细胞上的表达，包括来自 IAV 宿主物种和 IAV 研究中使用的动物的红细胞。这些 Sia 形式在不同动物之间差异很大，它们对 IAV NA 和 HA 活性以及细菌唾液酸酶（神经氨酸酶）的抑制作用表明在分泌的粘液中具有宿主变量的保护作用。