Grant: Operating Grant

We are interested in studying how viruses replicate and produce disease. A critical stage in viral replication is the activation of expression of viral proteins in infected cells. Surprisingly, the regulation of gene expression of human herpes virus (HSV) types 1 and 2 is not yet well understood. We have recently made two discoveries that strongly suggest a major mechanism for the activation of expression of most HSV genes. We propose now to continue our studies, to fully decipher the regulation of HSV gene expression and consequently of HSV replication. HSV are most prevalent human viruses that produce cold sores and genital infections but also major diseases such as encephalitis, stromal keratitis and disseminated neonatal infections. HSV-2 is also a critical risk factor in the transmission of HIV. Moreover, HSV-based vectors are currently being analyzed for their potential in gene therapy and as oncolytic agents. Expression of genes from the HSV genome is required for both applications. Our studies therefore not only directly address an important human pathogen but have also direct implications on the potential uses of HSV vectors in molecular medicine.