PATHOGENESIS AND CHEMOTHERAPY OF HERPES VIRUS INFECTIONS IN MAN

该项目的目标是描述发病机制，自然 人类疱疹病毒感染的历史、免疫学和治疗， 强调单纯疱疹病毒（HSV）和水痘-带状疱疹（VZV） 感染. 多年来，我们建立了价值，长期疗效 口服阿昔洛韦治疗和抑制复发性 生殖器疱疹和口腔疱疹。 我们定义了单纯疱疹病毒对阿昔洛韦耐药 免疫正常个体的感染。 我们研究了阿昔洛韦， 和Sorivudine作为带状疱疹的治疗，我们已经做了正式的 治疗带状疱疹后神经痛的研究。 当前的主要重点 该项目涉及HSV分子发病机制的研究， VZV潜伏期。 我们研究了HSV-1和HSV-2潜伏相关的作用， 成绩单。 我们已经设计了特定的重组病毒， 改变了HSV潜伏期转录本的表达， 这些突变体对病毒感染、潜伏期和 重新激活 我们通过各种方法来定量潜伏病毒的水平， 详细的分子技术 我们还研究了延迟， VZV在人体组织中的基因调控，并确定了目前4种中的2种 在潜伏期中表达的已知基因。 过去一年里，我们 进行了人类疱疹tpe-8血清流行病学的新研究 感染，已知与卡波西肉瘤有关。 另外我们 进行了一系列的免疫学研究，以确定宿主因素， 可以预测HSV和频繁复发的症状性疾病。 这些研究包括HLA单倍型分析以及 患者细胞在体外释放细胞因子。

The goals of this projects are to characterize the pathogenesis, natural history, immunology, and therapy of human herpes virus infections, with an emphasis on herpes simplex virus (HSV) and varicella-zoster (VZV) infections. Over the years we established the value, long term efficacy and safety of oral acyclovir for treatment and suppression of recurrent genital herpes and oral herpes. We defined acyclovir resistance in HSV infections in immunologically normal individuals. We studied acyclovir, and sorivudine as treatments for zoster and we have done in formal studies for treatment of postherpetic neuralgia. Major current emphases of the project involve studies of the molecular pathogenesis of HSV and VZV latency. We examine the role of HSV-1 and 2 latency-associated transcript. We have engineered specific recombinant viruses that are altered in their expression of the HSV latency transcripts and determine the impact of those mutants on virus infection, latency and reactivation. We quantitate levels of latent virus by a variey of detailed molecular techniques. We have also studied the latency and gene regulation of VZV in human tissues and defined 2 of the 4 currently known genes that are expressed in latency. Within the past year, we undertook novel studies of the seroepidemiology of human herpes tpe-8 infection, known to be associated with Kaposi's sarcoma. Also, we undertook a series of immunologic studies to define host factors that could predict symptomatic disease with HSV and frequent recurrences. These have involved HLA haplotype analyses as well as studies of cytokine release by patient cells in vitro.