Enveloped viruses encompass some of the most common human pathogens causing infections of different severity, ranging from no or very few symptoms to lethal disease as seen with the viral hemorrhagic fevers. All enveloped viruses possess an envelope membrane derived from the host cell, modified with often heavily glycosylated virally encoded glycoproteins important for infectivity, viral particle formation and immune evasion. While N-linked glycosylation of viral envelope proteins is well characterized with respect to location, structure and site occupancy, information on mucin-type O-glycosylation of these proteins is less comprehensive. Studies on viral glycosylation are often limited to analysis of recombinant proteins that in most cases are produced in cell lines with a glycosylation capacity different from the capacity of the host cells. The glycosylation pattern of the produced recombinant glycoproteins might therefore be different from the pattern on native viral proteins. In this review, we provide a historical perspective on analysis of viral glycosylation, and summarize known roles of glycans in the biology of enveloped human viruses. In addition, we describe how to overcome the analytical limitations by using a global approach based on mass spectrometry to identify viral O-glycosylation in virus-infected cell lysates using the complex enveloped virus herpes simplex virus type 1 as a model. We underscore that glycans often pay important contributions to overall protein structure, function and immune recognition, and that glycans represent a crucial determinant for vaccine design. High throughput analysis of glycosylation on relevant glycoprotein formulations, as well as data compilation and sharing is therefore important to identify consensus glycosylation patterns for translational applications.

中文翻译：

---

病毒糖基化的全球性方面

包膜病毒包含一些引起不同严重程度感染的最常见的人类病原体，从无症状或极少症状到病毒性出血热所见的致死性疾病。所有被包膜的病毒均具有来源于宿主细胞的被膜，并被经常被重度糖基化的病毒编码的糖蛋白修饰，这对于感染性，病毒颗粒形成和免疫逃逸都很重要。尽管就位置，结构和位点占用而言，病毒包膜蛋白的N-联糖基化已得到很好的表征，但有关这些蛋白的粘蛋白型O-糖基化的信息尚不全面。病毒糖基化的研究通常仅限于重组蛋白的分析，重组蛋白在大多数情况下是在糖基化能力不同于宿主细胞能力的细胞系中产生的。因此，产生的重组糖蛋白的糖基化模式可能与天然病毒蛋白上的模式不同。在这篇综述中，我们提供了分析病毒糖基化的历史观点，并总结了聚糖在包膜人病毒生物学中的已知作用。此外，我们描述了如何使用基于质谱的全局方法克服复杂的分析限制，以使用复杂的包膜病毒单纯疱疹病毒1型为模型来识别病毒感染的细胞裂解物中的病毒O-糖基化。我们强调，聚糖通常对蛋白质的整体结构，功能和免疫识别起着重要作用，并且聚糖代表了疫苗设计的关键决定因素。对相关糖蛋白制剂进行糖基化的高通量分析，