Understanding receptor binding and conformational activation of viruses

Enveloped viruses first bind to cellular receptors and then insert their genomes via a process of membrane fusion.

Prior evidence suggests that for some viruses, receptor binding serves primarily to attach the virus, whereas for others it either activates the viral fusion proteins directly or helps organize the membrane interface to facilitate fusion, but it has been extremely challenging to test these roles directly.

This project seeks to test the roles of cellular receptors on viral fusion protein activation, viral fusion kinetics, and the membrane interfacial chemistry underlying fusion.

We use DNA-lipid conjugates as synthetic tethers capable of attaching viruses to membranes without native cellular receptors present. We then employ single-virus fluorescence microscopy to measure individual fusion events and compare their time-courses.

We seek to identify viruses that demonstrate each of these roles for cellular receptors:  simple attachment, conformational activation, or clustering of proteins at the fusion interface, and characterize their activation mechanisms.

This will help us better understand the free-energy landscape of viral membrane fusion and the host membrane organization required to support or suppress it.