THE PATHOGENESIS AND CHEMOTHERAPY OF HERPES VIRUS INFECTIONS IN MAN

该项目的目标是描述疾病的发病机制， 单纯疱疹病毒和单纯疱疹病毒的自然历史和治疗 水痘带状疱疹病毒感染。我们的临床重点一直是 诺曼人和免疫受损患者的生殖器疱疹。分析 无环鸟苷五年抑制性治疗频发的患者 复发的疱疹已经表明这种药物仍然有效， 耐受性好，不会引起耐药性。我们已经展示了 第一次，通过长时间的观察，一些人 降低他们的疱疹复发率，不再保证 慢性抑制疗法。我们继续利用我们的人类 复发性单纯疱疹病毒感染模型。我们是 对紫外线和其他物理现象进行详细研究 以及导致皮肤反复感染的化学诱因。的公开试验 旨在阻止诱导重新激活的药物已经被 已启动。阿昔洛韦封闭治疗的安慰剂对照试验 紫外线诱导的复活即将完成。我们还有 启动一项阿昔洛韦抑制的安慰剂对照试验 经常自发性复发的口腔疱疹。 我们实验室在这个项目中所做工作的主旨是 人三叉神经节单纯疱疹病毒潜伏期分析 利用原位杂交，我们最近展示了一类新的 潜伏感染人单纯疱疹病毒基因组转录的RNA 神经节。我们现在可以通过Northern检测到这些延迟的记录 杂交分析也是如此。最近的详细研究表明 确定了三个延迟转录，其末端比 准确绘制了地图。因为这些都非常重要 为了了解人类单纯疱疹病毒感染，我们开始了一个 一系列项目，目的是确定以下行动机制 潜伏期相关基因。

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.