THE PATHOGENESIS AND CHEMOTHERAPY OF HERPES VIRUS INFECTIONS IN MAN

该项目的目标是表征发病机制，自然 单纯疱疹病毒（HSV）和水痘-带状疱疹历史与治疗 病毒（VZV）感染。 我们的临床重点一直是口服和 生殖器疱疹和带状疱疹。 10年抑制性阿昔洛韦治疗分析 治疗经常复发的疱疹患者的药物显示， 保持有效和良好的耐受性。 我们开发并继续测试 一个模型系统，其中紫外线诱导复发性口腔或骶骨 人类的HSV感染 在安慰剂对照试验中， 发现防晒剂和无环鸟苷能显著防止紫外线诱导的 HSV感染的复发。 我们现在正在研究局部辣椒素， 物质P消耗剂，以确定它是否会防止复发 口腔疱疹 一项安慰剂对照试验表明，口服阿昔洛韦 显著降低了HSV 1在频繁感染患者中的爆发率， 口腔复发 我们实验室的主要基础研究方向是 HSV和VZV潜伏期和发病机制的分子方面。 期间 去年，我们完成了一系列研究， HSV 2潜伏期相关基因的基因。 突变病毒只缺少 该基因的启动子被证明可以诱导典型的生殖器疱疹， 豚鼠，但有明显较低的可能性重新激活。 还检查了参与潜伏期和调节的特定VZV基因。 基因29和62在人类神经节中表达。 发起人，成绩单 这些基因和VZV基因4、10、28、61和63的调控正在进行中。 研究了

The goals of the project ar to characterize the pathogenesis, natural history and therapy of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Our clinical emphasis has been on oral and genital herpes and zoster. Analysis of 10 years of suppressive acyclovir therapy in patients with frequently recurring herpes have shown the drug to remain effective and well-tolerated. We developed and continue to test a model system in which ultraviolet light induces recurrent oral or sacral HSV infections in humans. In placebo-controlled trials topical sunblockers and acyclovir were found to significantly prevent uv-induced reactivation of HSV infection. We are now studying topical capsaicin, a substance P depleting agent to determine whether it will prevent recurrent oral herpes. A placebo-controlled trial showed that oral acyclovir significantly reduces rates of HSV1 outbreaks in patients with frequent oral recurrences. The major basic research thrust of our laboratory has been to define molecular aspects of HSV and VZV latency and pathogenesis. During the past year we completed one series of studies examining the nature and role of the latency-associated gene of HSV2. Mutant virus lacking only the promoter for this gene was shown to induce typical genital herpes in guinea pigs, but to have a markedly lower likelihood of reactivating. Specific VZV genes involved in latency and regulation are also examined. Genes 29 an 62 are expressed in human ganglia. The promoters, transcripts and regulation of these genes and VZV genes 4, 10, 28, 61 and 63 are being studied.