Neal A. DeLuca, PhD

The pathogenic and cytotoxic effects of viruses are largely due to the expression of viral gene products. The expression of the Herpes Simplex Virus (HSV) is influenced by host defense mechanisms that repress expression, and by viral transacting proteins that promote expression. The interplay between the two determines the outcome of infection; whether the infection is productive, abortive, or latent. A hallmark of productive HSV infection is the sequential and coordinately regulated expression of the approximately 90 genes. Five genes are expressed before viral protein synthesis. These encode proteins that overcome host antiviral mechanisms, as well as proteins that activate viral gene expression by several mechanisms. One protein, ICP4, activates the transcription of genes involved in viral genome replication, as well as genes encoding proteins involved in capsid assembly and the virion itself. These processes all involve dynamic interactions between cellular and viral proteins, and the cell and viral genome.

We study the virus-cell interactions affecting HSV gene expression. These studies focus on, i. how the virus overcomes cellular silencing mechanisms, ii. the mechanisms by which viral transacting proteins, including ICP4, create a transcriptional environment that promote prolific viral transcription and host cell shutoff, and iii. how viral DNA replication is coupled to viral transcription. To undertake these studies we combine molecular genetic approaches to modify trans and cis acting elements involved in the virus cell interactions, along with contemporary genomic and proteomic approaches to gain a comprehensive and unbiased view of the virus-cell interactions affecting HSV gene expression.