Fellowship Will Allen: Regulation of Apoptosis by the Herpes Simplex Virus Latency Associated Transcript

SpecijicAim: Test the hypothesis that LATpromotes survival by regulating apoptosis. HSV Infection. HSV-1 is one of eight herpes viruses that infect humans. Following productive infection of epithelium, HSV-1 enters Viral Infection Anll-Apoplosls Gene all Necrosis g dendritic termini and travels axonally to regional sensory ganglia5.7 where the neuron can host a permissive or nonpermissive infection. The fate of the neuron depends on several factors (Fig. 1) including the initial viral load, efficiency of virus replication, synthesis and expression of the Cell Death (EpilheliaICell) anti-apoptosis (ICP4, ICP27, "(34.5, Us3, gJ) and neurovirulence ("(34.5) Cell Survival (Neuron) genes8.IO as well as the immune response. II If the host and viral factors Figure 1. LAT may function as 1. antisense, 2. to block cell toxicity, or 3. to block apoptosis. limit the virus' ability to replicate12 and the cell's ability to undergo apbptoslS,13 viral DNA enters the neuronal nucleus where latency is established. Viral latency is characterized by the presence of an intact, non-replicating viral genome in an infected cell that evades immunosurveillance. Although cryptic, the latent viral genome has the ability to reacti vate. \ 1,14 Preferable sites of latency are sensory neurons. 5,7.14-21