The virus envelope glycoprotein orchestrates entry of the virus into its target cell by mediating attachment to cell-surface receptors and fusion of the virus and cell membranes. As such, these glycoproteins provide fertile ground for study towards the development of antiviral agents and vaccines. My laboratory is interested in cellular, molecular, and structural aspects of virus assembly and entry.

The recent focus of my lab has been on the envelope glycoprotein (GPC) of the Arenaviruses, a little-studied family of rodent-borne viruses responsible for hemorrhagic fevers worldwide (Lassa fever in Africa, and South American hemorrhagic fevers in the New World). Over the past several years, we have characterized the unusual GPC complex. In addition to the receptor-binding and transmembrane fusion subunits common to all Class I envelope glycoproteins, GPC retains a cleaved and stable signal peptide (SSP) as an essential element. On the cytoplasmic face of GPC, SSP likely forms an intersubunit zinc-finger structure with the transmembrane subunit and functions in intracellular transport of GPC to the cell surface, and in virion assembly. The ectodomain of SSP interacts with the ectodomain of the transmembrane fusion subunit to modulate low pH-induced activation of membrane fusion, which takes place in the maturing endosome of the cell. This interaction provides the basis for fusion inhibition by structurally diverse small-molecule antiviral compounds and may be involved in vaccine attenuation. Genetic and structural studies are underway to better understand this critical viral target for antiviral and vaccine development.