UNIVERSITY OF ILLINOIS
The g134.5 protein, present in herpes simplex viruses (HSV), plays an essential role in viral virulence. Unlike wild-type virus, HSV mutants that lack the g134.5 gene are incapable of replicating and causing diseases. However, the underlying mechanisms are incompletely understood. The major goal of the proposed research is to investigate the biological functions of g134.5 during HSV infection. HSV g134.5 contains an amino-terminal domain, a linker region of triplet repeats, and a carboxyl-terminal domain. A critical function of g134.5 is to block the interferon response mediated by double-stranded RNA dependent protein kinase PKR. In addition, g134.5 is involved in virus maturation. This activity maps to the amino-terminus of g134.5 that shuttles between the nucleus, nucleolus and cytoplasm. It is thought that coordinated actions of functional elements in the g134.5 protein and cellular factors facilitate viral replication that contributes to viral virulence. To test this hypothesis, mutational analysis will be performed to define functional modules of g134.5. Recombinant viruses will be constructed to study viral replication, spread, and the interferon response in infected cells. Experiments will also be performed to identify targets of g134.5. Furthermore, studies will be carried out to explore the molecular nature by which g134.5 promotes viral infection. Taken together, these studies will provide insights into the mechanisms of HSV pathogenesis, which may lead to the development of novel vaccines and antiviral therapeutics.