Structure as a Key to Herpesvirus Entry
We are structural biologists interested in various aspects of viral lifecycle. Our favorite viruses are herpesviruses because they are ancient, marvelously complex viruses that are also important human pathogens. In our work, we are guided by conviction that to fully understand the mechanism of any biological process, one must know the structures of participating macromolecules.
Our work intends to answer the following broad questions. How do herpesviruses enter cells to initiate infection? How do herpesviruses assemble and get out of the cells once they have replicated? How do herpesviruses establish latency, a dormant state that allows herpesviruses to establish persistent, lifelong infections? Although herpesviruses are our main interest, we are also pursuing some other viruses; one question we ask is how do avian retroviruses enter cells.
Figure 1. HSV Entry Machinery - How do 4 Proteins Work Together? While most enveloped viruses use a single protein to effect viral entry, herpesviruses use several glycoproteins.
All of the above processes are complex and involve multiple proteins. To understand how these proteins work together to bring about viral entry or egress, we use a structural approach. The main tool we use is x-ray crystallography, which allows us to determine 3D structures of the proteins of interest at the level of atoms. We also use other structural techniques such as NMR and EM, when necessary. The structures provide close-up views of the architecture of these proteins and often shed light on how proteins function. But structures do not necessarily nail down the answers to all lingering questions. More often, structures hold many surprises and, importantly, enable us to ask new, better-articulated questions regarding the mechanism. To answer these mechanistic questions, we use biochemical, structural, and cellular techniques.
Figure 2. Crystals of viral glycoproteins obtained in our lab.
Figure 3. Crystal structure of glycoprotein B (gB), a key player in the entry of herpes simplex virus type 1.