Department of Biology and Microbiology, South Dakota State University, Brookings, SD, 57007, USA.
Department of Chemistry, University of California, Davis, CA, 95616, USA.
Virology. 2020 Jun;545:16-23. doi: 10.1016/j.virol.2020.02.007. Epub 2020 Mar 3.
Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other mammalian hosts. By using traditional hemagglutination assay coupled with sialoglycan microarray (SGM) platform and functional assays, we demonstrated that IDV is more efficient in recognizing both 9-O-acetylated N-acetylneuraminic acid (Neu5,9Ac) and 9-O-acetylated N-glycolylneuraminic acid (Neu5Gc9Ac) than influenza C virus (ICV), a ubiquitous human pathogen. ICV seems to strongly prefer Neu5,9Ac over Neu5Gc9Ac. Since Neu5Gc9Ac is different from Neu5,9Ac only by an additional oxygen in the group at the C5 position, our results reveal that the hydroxyl group in Neu5Gc9Ac plays a critical role in determining receptor binding specificity, which as a result may discriminate IDV from ICV in communicating with 9-O-acetylated SAs. These findings shall provide a framework for further investigation towards better understanding of how newly discovered multiple-species-infecting IDV exploits natural 9-O-acetylated SA variations to expand its host range.
牛源狄氏副流感病毒（IDV）作为主要的天然宿主库，可周期性地溢出感染其他哺乳动物宿主。本研究通过传统血凝试验结合唾液酸糖脂微阵列（SGM）平台和功能分析，证实与普遍存在的人类病原体丙型流感病毒（ICV）相比，IDV 能更有效地识别 9-O-乙酰化 N-乙酰神经氨酸（Neu5,9Ac）和 9-O-乙酰化 N-羟乙酰神经氨酸（Neu5Gc9Ac）。ICV 似乎更倾向于 Neu5,9Ac 而不是 Neu5Gc9Ac。由于 Neu5Gc9Ac 与 Neu5,9Ac 仅在 C5 位的基团上多一个氧原子不同，我们的结果表明 Neu5Gc9Ac 中的羟基在决定受体结合特异性方面起着关键作用，这可能导致 IDV 在与 9-O-乙酰化 SA 相互作用时与 ICV 区分开来。这些发现为进一步研究新发现的多宿主感染的 IDV 如何利用天然 9-O-乙酰化 SA 变异来扩大其宿主范围提供了框架。
