Glycan-mediated enhancement of reovirus receptor binding

Viral infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and their cell surface receptors. Despite recent progress, the molecular mechanisms underlying the multistep reovirus entry process are poorly understood. Using atomic force microscopy, we investigated how the reovirus sigma 1 attachment protein binds to both alpha-linked sialic acid (alpha-SA) and JAM-A cell-surface receptors. We discovered that initial sigma 1 binding to alpha-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following alpha-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of alpha-SA. Since ISVPs have an extended sigma 1 conformer, this finding suggests that alpha-SA binding triggers a conformational change in sigma 1. These results provide new insights into the function of viral attachment proteins in the initiation of infection and open new avenues for the use of reoviruses as oncolytic agents.