Viruses engage with host cell membrane receptors through highly specific interactions to initiate infection, yet the molecular mechanisms governing viral binding, detachment, and mobility for many viruses still remain ambiguous. In this study, we investigate these processes for Sendai virus (SeV), a well-established model virus in the Paramyxoviridae family. SeV binding is mediated by the hemagglutinin-neuraminidase (HN) glycoprotein, which possesses both receptor-binding (hemagglutinin) and receptor-cleaving (neuraminidase) activity targeting sialic acid receptors. To study the role of neuraminidase activity on SeV binding, detachment, and mobility, we use single-virus assays with supported lipid bilayers (SLBs) as target membranes in conjunction with a fluorescence spectroscopy-based neuraminidase activity assay. We find that while neuraminidase activity is suppressed under physiological pH (7.4) compared to acidic pH (5.5), SeV binding is consistent between the two conditions, indicating that neuraminidase activity is not required for receptor binding. On the other hand, detachment measurements reveal that while neuraminidase activity does affect the extent to which detachment can occur, substantial detachment still occurs under neuraminidase-suppressed conditions. This suggests a potential neuraminidase-independent detachment pathway, and we discuss a mechanism whereby viral mobility may facilitate detachment under conditions where cleavage activity is reduced. We also explore the use of small molecule neuraminidase inhibitors to probe the effect of neuraminidase activity on viral attachment, detachment, and mobility.
Bai et al. (Sun,) studied this question.