Joost Snijder

Surface antigens of enveloped viruses are notoriously heavily glycosylated. Besides their role in receptor binding and host cell attachment, the glycans on viral envelope proteins are thought to have a steric shielding effect on interactions with neutralizing antibodies of the host immune system. The glycans of viral envelope proteins represent challenging targets in structural studies, due to their inherent heterogeneity and flexibility. However, recent advances in glycoproteomics and cryo electron microscopy enable a more comprehensive analysis of glycosylation in viral envelope proteins. Glycoproteomics can be used to survey site-specific glycosylation patterns with the aid of new fragmentation techniques, capable of detecting several dozens of unique glycan compositions per glycosylation site from complex mixtures. These surveys of glycan composition complement detailed structural studies of the antigens by cryoEM, aiding model building and providing a better understanding of antigen-antibody interactions. Applications of this integrated structural biology approach will be discussed following examples of human coronaviruses, HIV, and Epstein-Barr Virus. These studies reveal a dual role for viral N-linked glycans in antigen-antibody interactions, as some provide a steric shielding effect, while others form an integral part of the epitope and appear to play a crucial role in neutralization mechanisms.