Lucas Taryn M, Gupta Chitrak, Altman Meghan O, Sanchez Emi, Naticchia Matthew R, Gagneux Pascal, Singharoy Abhishek, Godula Kamil
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093.
School of Molecular Sciences, Arizona State University, Tempe, AZ 85281.
Chem. 2021 Dec 9;7(12):3393-3411. doi: 10.1016/j.chempr.2021.09.015. Epub 2021 Oct 22.
Influenza A viruses (IAVs) exploit host glycans in airway mucosa for entry and infection. Detection of changes in IAV glycan-binding phenotype can provide early indication of transmissibility and infection potential. While zoonotic viruses are monitored for mutations, the influence of host glycan presentation on viral specificity remains obscured. Here, we describe an array platform which uses synthetic mimetics of mucin glycoproteins to model how receptor presentation and density in the mucinous glycocalyx may impact IAV recognition. H1N1 and H3N2 binding in arrays of α2,3- and α2,6-sialyllactose receptors confirmed their known sialic acid-binding specificities and revealed their different sensitivities to receptor presentation. Further, the transition of H1N1 from avian to mammalian cell culture improved the ability of the virus to recognize mucin-like displays of α2,6-sialic acid receptors. Support vector machine (SVM) learning efficiently characterized this shift in binding preference and may prove useful to study viral evolution to a new host.
甲型流感病毒（IAV）利用气道黏膜中的宿主聚糖进行侵入和感染。检测IAV聚糖结合表型的变化可以为传播性和感染潜力提供早期指示。虽然对人畜共患病毒的突变进行了监测，但宿主聚糖呈现对病毒特异性的影响仍不明确。在这里，我们描述了一种阵列平台，该平台使用粘蛋白糖蛋白的合成模拟物来模拟粘液糖萼中受体的呈现和密度如何影响IAV识别。H1N1和H3N2在α2,3-和α2,6-唾液酸乳糖受体阵列中的结合证实了它们已知的唾液酸结合特异性，并揭示了它们对受体呈现的不同敏感性。此外，H1N1从禽类细胞培养向哺乳动物细胞培养的转变提高了病毒识别α2,6-唾液酸受体粘蛋白样展示的能力。支持向量机（SVM）学习有效地表征了这种结合偏好的转变，可能对研究病毒向新宿主的进化有用。
