THE PATHOGENESIS AND CHEMOTHERAPY OF HERPES VIRUS INFECTIONS IN MAN

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The goals of the project are to characterize the pathogenesis, the natural history and the therapy of herpes simplex virus and varicella zoster virus infections. Our clinical emphasis has been on genital herpes in norman and immune-impared patients. Analysis of five years of suppressive acycloviar in patients with frequently recurring herpes have shown the drug to remain effective, to be well tolerated, and to not induce drug resistance. We have shown for the first time that with prolonged observation some individuals diminish their rates of herpetic recurrences and no longer warrant chronic suppressive therapy. We continue to utilize our human model of recurrent herps simplex virus infection. We are conducting detailed studies of ultraviolet light and other physical and chemical inducers of recurrent skin infection. Open trials of agents designed to block the induced reactivation have been initiated. A placebo-controlled trial of acyclovir for blocking ultra-violet induced reactivation is nearly complete. We have also initiated a placebo-controlled trial of acyclovir for suppression of frequent spontaneously recurring oral herpes. The major thrust of our laboratory effort in this project has been the analysis of herpes simplex latency in human trigeminal ganglia using in situ hybridization we recently demonstrated a novel class of RNAs transcribed from the HSV genome in latently infected human ganglia. We can now detect these latency transcripts by northern hybridization analysis as well. Recent detailed studies have identified three latency transcripts whose termini have been more accurately mapped. Because of the great importance of these findings for an understanding of human HSV infection, we began a series of projects aimed at identifying the mechanism of action of the latency associated gene.