THE PATHOGENESIS AND CHEMOTHERAPY OF HERPES VIRUS INFECTIONS IN MAN

该项目的目标是描述发病机制， 单纯疱疹病毒的治疗方法 水痘带状疱疹病毒感染。 我们的临床重点是 对正常人和免疫缺陷患者生殖器疱疹的影响。 分析 五年的抑制性阿昔洛韦在患者中经常 复发性疱疹显示药物仍然有效， 耐受性良好，并且不诱导耐药性。 我们已经表明 经过长时间的观察， 降低疱疹复发率，不再需要 慢性抑制疗法 我们继续利用我们的人力资源 复发性单纯疱疹病毒感染模型。 我们 对紫外线和其他物理现象进行详细的研究 和复发性皮肤感染的化学诱导物。 公开审判 设计用于阻断诱导再激活的药物已经被 启动。 无环鸟苷阻断的安慰剂对照试验 紫外线诱导的再活化几乎完全。 我们还 启动了一项安慰剂对照试验， 口腔疱疹频繁复发的症状 在这个项目中，我们实验室的主要工作是 单纯疱疹病毒在三叉神经节潜伏期分析 利用原位杂交，我们最近证明了一类新的 从潜伏感染的人类HSV基因组转录的RNA 神经节 我们现在可以通过北方检测这些潜伏期转录本 杂交分析。 最近的详细研究表明， 发现了三个潜伏期转录本，它们的末端更多地 准确地映射。 由于这些问题的重要性， 为了了解人类HSV感染的发现，我们开始了一项 一系列项目，旨在确定 潜伏相关基因

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.