THE PATHOGENESIS AND CHEMOTHERAPY OF HERPES VIRUS INFECTIONS IN MAN

该项目的目标是描述发病机制，自然 单纯疱疹病毒和水痘-带状疱疹病毒历史与治疗 感染.我们的临床重点一直是生殖器疱疹在正常和 免疫力受损的患者。无环鸟苷抑制性治疗老年人6年疗效分析 经常复发的疱疹患者显示药物仍然存在 有效、耐受性好且不诱导耐药性。我们 继续研究紫外线和其他物理和 诱导人类复发性单纯疱疹感染的化学试剂。一 阿昔洛韦阻断u-v诱导的安慰剂对照试验 重新激活几乎完成。我们还启动了一个安慰剂对照的 无环鸟苷抑制多发性自发复发性 口腔疱疹 在这个项目中，我们实验室工作的主要重点是 人类神经节中单纯疱疹潜伏期的分析。我们证明了HSV-1 三叉神经节潜伏期相关RNA和骶神经节HSV-2 RNA 神经节在过去的一年里，引物延伸分析，测序和 CAT构建体的转染用于进一步确定结构， 动力学和这些潜伏相关RNAS的调节。推定的 已鉴定了“变体”启动子。

The goals of the project are to characterize the pathogenesis, natural history and therapy of herpes simplex virus and varicella-zoster virus infections. Our clinical emphasis has been on genital herpes in normal and immune-impaired patients. Analysis of six years of suppressive acyclovir in patients with frequently recurring herpes have shown the drug to remain effective, to be well tolerated, and to not induce drug resistance. We continue to study the ability of ultraviolet light and other physical and chemical agents to induce recurrent herpes simplex infections in humans. A placebo-controlled trial of acyclovir for blocking, u-v induced reactivation is nearly complete. We 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 ganglia. We demonstrated HSV-1 latency-associated RNAs in trigeminal ganglia and HSV-2 RNAs in sacral ganglia. During the past year primer extension analyses, sequencing and transfections of CAT constructs were used to further define the structure, kinetics, and regulation of these latency-associated RNAS. A putative "variant" promoter has been identified.