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Glycan-mediated enhancement of reovirus receptor binding.

Nature communications (2019-10-03)
Melanie Koehler, Pavithra Aravamudhan, Camila Guzman-Cardozo, Andra C Dumitru, Jinsung Yang, Serena Gargiulo, Patrice Soumillion, Terence S Dermody, David Alsteens
ABSTRACT

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 σ1 attachment protein binds to both α-linked sialic acid (α-SA) and JAM-A cell-surface receptors. We discovered that initial σ1 binding to α-SA favors a strong multivalent anchorage to JAM-A. The enhanced JAM-A binding by virions following α-SA engagement is comparable to JAM-A binding by infectious subvirion particles (ISVPs) in the absence of α-SA. Since ISVPs have an extended σ1 conformer, this finding suggests that α-SA binding triggers a conformational change in σ1. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3′-N-Acetylneuraminyl-N-acetyllactosamine sodium salt, ≥95%
Sigma-Aldrich
Nitrilotriacetic acid disodium salt, Sigma Grade, ≥99%
Sigma-Aldrich
Anti-JAM-A antibody, Mouse monoclonal, clone J10.4, purified from hybridoma cell culture