With this award, the Chemistry of Life Processes Program in the Division of Chemistry and the Genetic Mechanisms Cluster in the Division of Molecular and Cellular Biosciences are funding Dr. Alex Evilevitch from Carnegie Mellon University to investigate the mechanism by which a virus infects its host. This research project is directed at the study of the physical-chemical mechanisms essential for infectivity and replication of viruses. The findings are of fundamental importance for virology and physical virology in general. Specifically, this project will provide new insight into physical conditions necessary for the successful delivery of a virus genome into the cell nucleus and for the subsequent process of assembly of new virus particles within the cell. This project will expose undergraduate students to biophysical research methods.
Herpes Simplex virus type 1 (HSV-1) is a prototypical model system to study the general infection mechanisms of herpesviruses and other viruses that release their genome into the cell nucleus without capsid disassembly. During viral replication, an ATP-dependent motor packages the viral genome into a preformed capsid through a unique opening created by the portal complex. Between rounds of replication, the virion must be sufficiently stable to ensure that the packaged genome is retained within the capsid. Conversely, during infection, the virion must be unstable enough to allow genome release into the cell nucleus. A precise balance between these physical aspects of the viral capsid and its encapsidated genome is crucial to the viral replication cycle. Using HSV-1 as the primary model system, this project will investigate the roles of intracapsid DNA mobility, internal DNA pressure and capsid stability for viral replication with respect to retention of the packaged genome inside the capsid and its subsequent ejection during infection. These studies aim to provide new insights into the key mechanisms facilitating, as well as inhibiting, viral infectivity.
