S-layer architecture and glycosylation and their role in shaping virus–host specificity in prokaryotes

The crystalline surface layer (S-layer) of prokaryotes constitutes a critical macromolecular interface governing virus-host interactions. In this review, we synthesize recent findings regarding the role of S-layer glycoproteins as viral receptors, examine the structural and functional diversity of these systems across prokaryotic lineages, and analyze the molecular strategies that determine virus-host specificity. By integrating perspectives from structural biology, microbiology, and evolutionary studies, we seek to elucidate the fundamental principles and emerging themes that characterize virus-host interactions at the cell surface mediated by the S-layer.