Herpes simplex virus type 1 (HSV-1) can establish either a lytic or latent infection in neurons. Latency persists until the virus reactivates and creates a productive infection. This proposal is aimed at elucidating molecular mechanisms involved in reactivatation from latency and subsequent establishment of productive infection in neurons. During latent infection nearly all viral gene expression is dormant. The only viral gene expressed during latency is that encoding the latency associated transcripts (LAT). Downregulation of LAT coincides with reactivation as well as expression of the viral immediate early (IE) genes. The IE genes encode transcriptional regulators that participate in the temporal cascade leading to the establishment of productive infection. Numerous stimuli result in reactivation from latency by activating second messenger pathways which ultimately alter the expression of LAT and the IE genes. The purpose of this study is to characterize the effects of signaling pathways on cellular and HSV-1 gene expression and how this relates to viral reactivation. The proposal focuses on the relationship between LAT expression and the cellular transcription factor, Inducible cAMP Early Repressor (ICER). ICER is a powerful transcriptional repressor that is expressed in response to stress and other stimuli via phosphorylation of CREB. ICER is not regulated by post-translational modifications, and its abundance dictates activity. The focus of this proposal is to determine the role of ICER on LAT expression and HSV-1 reactivation. The specific goals of this proposal are (1) to characterize the transcriptional regulation of LAT by ICER, and (2) to examine the relationship between ICER and temporal cascade leading to HSV-1 reactivation in a primary neuronal latency model.
| Colgin, M A; Smith, R L; Wilcox, C L (2001) Inducible cyclic AMP early repressor produces reactivation of latent herpes simplex virus type 1 in neurons in vitro. J Virol 75:2912-20 |
