The work in my laboratory focuses on structural analysis of the complex cell-entry machinery of herpesviruses with the ambition to develop a “molecular movie” illustrating successive steps during entry. Herpesviruses are a family of human pathogens, such as Herpes Simplex virus, cytomegalovirus, and Epstein-Barr virus, that infect their hosts for life, causing cold sores, blindness, encephalitis, cancers, and life-threatening conditions in immunocompromised individuals. Knowing the detailed mechanism of their entry into cells may lead to the design of antiviral therapeutics. In our research, we use X-ray crystallography with contributions from other biophysical and biochemical techniques.

The mechanism by which herpesviruses enter cells remains poorly understood likely due to its complexity. While most enveloped viruses use a single viral protein to effect cell entry, all herpesviruses require at least three conserved proteins: gB, gH, and gL. These three proteins are thought to carry out the fusion of viral and cell membranes – a process at the core of viral entry – but their precise functions are unknown. Recently, we determined the atomic-level structure of gB, the most conserved component of herpesvirus membrane-fusion apparatus, from Herpes Simplex virus. The structure pinpointed gB as the fusion protein, but its function remains puzzling because gB is unable to carry out membrane fusion on its own. In all herpesviruses, gB requires contributions from gH/gL complex plus, in some herpesviruses, from a receptor-binding protein as well. We are interested in determining how gB and gH/gL work together to accomplish membrane fusion and how the signal from the receptor-binding protein triggers the membrane-fusion apparatus. Our approach combines determining the structures of individual proteins with studying their interactions during cell entry.