Influenza virus infections cause a wide variety of outcomes, from mild disease to 3 to 5 million cases of severe illness and ∼290,000 to 645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose-dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity.

流感病毒感染导致各种各样的结果，从轻度疾病到3到500万例严重疾病，全世界每年约有290,000到645,000例死亡。目前尚不清楚这些不同结果的分子机制。人宿主内的糖基化在流感病毒生物学中起关键作用。但是，尚未研究这些修饰对流感疾病严重程度的影响。在这里，我们使用雪貂模型和我们的凝集素微阵列技术，将糖原宿主对流感病毒感染的反应作为疾病严重程度的函数。我们确定聚糖表位高甘露糖为流感病毒诱导的发病机理和疾病后果严重程度的标志。高甘露糖的诱导取决于未折叠的蛋白质反应（UPR）途径，先前显示与肺损伤和流感病毒感染严重程度有关的途径。此外，甘露聚糖结合凝集素（MBL2）是一种对流感结果产生负面影响的先天性免疫凝集素，它以高度依赖于甘露糖的方式识别感染了流感病毒的细胞。总之，我们的数据认为，高甘露糖基序是宿主细胞上与感染相关的分子模式，可指导免疫反应，导致与严重性相关的损害。