This investigation is committed to elucidate the relationship between neuronal protein synthesis, anterograde axonal transport (AAT), and herpes simplex virus (type I; HSV) latency (and reactivation) during recurrent HSV infection of the eye. The final objective is to devise some method to interrupt, control or prevent HSV reactivation, replication, or AAT based on knowledge of these relationships. In this initial stage, basic information on (a) the characteristics of the synthesis and subsequent AAT of neuronal proteins, and (b) some physiological factors that influence these activities will be obtained utilizing the corneal-trigeminal system of healthy, uninfected rabbits. It is hypothesized that HSV latency and reactivation in trigeminal ganglion (TG) are controlled by the dynamic interactions between various viral and host factors which are directly or indirectly exerted on the infected neurons. The final effect of these complex interactions is to act on neuronal protein synthesis, which in turn affects HSV replication. Thus, neuronal protein synthesis and AAT is suitable as a common indicator of the final effects caused by various factors that influence HSV and may provide a strategic step for intervening HSV replication during reactivation. The following studies for testing the hypothesis will be performed. (A) The synthesis and AAT of TG proteins of previously unmanipulated rabbits will be characterized. Neuronal proteins will be labeled by radioisotope technique. The parameters to be studied will include rate of synthesis, turnover time, composition of synthesized proteins, type and percentage of proteins undergoing AAT, and the rates of AAT. Standard biochemical techniques of liquid scintillation counting and polyacrylamide gel electrophoresis will be used. (B) The synthesis and AAT of neuronal proteins in TG will be determined in healthy rabbits following manipulations (electrical stimulation and epinephrine iontophoresis) known to induce HSV shedding. Subtle changes in the parameters being evaluated will be detected by comparison to the previous group of animals. Experiments in these studies are designed with consideration of specific needs relevant to their application to future subsequent studies on HSV-infected rabbits (e.g. to determine the spatial and temporal integrations of HSV-replication and TG protein synthesis and AAT during HSV reactivation). These studies may provide new information relevant to the clinical treatment of recurrent ocular HSV infection.
