Deborah Parris

Focus

Herpes simplex virus replication; DNA synthesis

Research interests

Herpes simplex virus (HSV) is one of the most complex of the animal viruses encoding more than 80 different genes. Despite its complexity, it is the easiest member of the herpes virus family with which to work and has proven to be a good model system to study functions related to viral replication.

In my laboratory, we are studying the process of HSV DNA replication for two reasons: 1.This process represents an excellent target for the development of antiviral compounds against this important family of viruses; and 2.The virus encodes many of the genes involved in DNA replication and, therefore, is a good model system for studying this process in eukaryotes. We are currently studying two HSV proteins directly involved in viral DNA replication and a third protein which interacts with the DNA replication proteins. A combination of molecular and biochemical techniques and high level heterologous expression systems are being used to understand the functions of these proteins. One of these, UL42, is the DNA polymerase (pol) accessory which renders the pol fully processive. We are identifying the functional domains required for physical and functional interaction with the pol and the mechanism by which it increases processivity. UL9 is another essential DNA replication protein which binds to origins of replication, possesses limited helicase activity, and presumably initiates the process of DNA replication in infected cells. Recently we demonstrated that UL9 also binds to UL42 and we have mapped the interaction site to the amino terminus of UL9. Studies are underway to examine the functional significance of this interaction using in vitro and in vivo assays. The third protein possesses DNase activity and interacts with several proteins which are required for DNA replication, but its function in virus replication remains unknown. Structure-function analysis reveals that the same sequences required for nuclease activity in vitro are also required for virus replication in vivo. Viral mutants are being constructed to better determine how lack of nuclease function affects virus replication.

Publications

• Thornton, K.E., Chaudhuri, M., Monahan, S.J., Grinstead, L.A., and Parris, D.S. Analysis of in vitro activities of herpes simplex virus type 1 UL42 mutant proteins: Correlation with in vivo function. Virology, in press, 2000.
• Monahan, S.J., Grinstead, L.A., Olivieri, W., and Parris, D.S. Interaction between the herpes simplex virus type 1 origin-binding and DNA polymerase accessory proteins. Virology, 241: 122-130, 1998.
• Henderson, J.O., Ball-Goodrich, L.J., and Parris, D.S. Structure-function analysis of the herpes simplex virus type 1 deoxyribonuclease: Correlation of nuclease activity in vitrowith replication function in viral-infected cells. Virology, 243:247-259, 1998.