TRIGEMINAL NEUROBIOLOGY--REACTIVATION OF LATENT HSV-1

单纯疱疹病毒(HSV)感染包括几个不同的阶段； 即初次感染、潜伏感染和潜伏感染的重新激活 病毒产生反复发作的疾病。口腔单纯疱疹病毒感染(疱疹 唇肌)，三叉神经节是潜伏感染的部位。 由于估计有很大一部分人口患有潜伏的HSV 感染，因为反复感染可能是最大的 单纯疱疹病毒的蓄水池，努力控制病毒的重新激活，因此 反复感染对控制艾滋病的传播极为重要。 人群中的病毒。单纯疱疹病毒潜伏和感染的确切机制(S) 再激活包括免疫、神经和内分泌的作用 系统在很大程度上是未知的。旨在解开相互作用的研究 以及这些不同系统在病毒重新激活中的作用 需要三叉神经节才能进行有效的干预 都是设计好的。研究HSV重新激活所需的最重要的工具 是一个很好的动物模型，不幸的是，目前还不存在。这个 这项研究计划的主要目标是建立一种动物模型 三叉神经节潜伏HSV-1的再激活系统 老鼠。使用建立良好的小鼠角膜模型研究HSV潜伏期、病毒 重新激活将使用各种应激源，包括 感染小鼠肝炎病毒或鼠伤寒沙门氏菌； 免疫抑制药物环磷酰胺和环孢素A；总则 麻醉；暴露于亚红斑剂量的紫外线 辐射。病毒的重新激活将通过监测HSV- 特异性免疫球蛋白，细胞毒性T细胞活性，分离 小鼠传染性病毒与单纯疱疹病毒特异性蛋白的存在 纸巾。利用这一模式系统，将进行额外的研究，以 分析免疫T细胞的作用，以及细胞因子白介素1(IL1)， IL-2、IL-6、肿瘤坏死因子-α、干扰素-γ (IFNGamma)和转化生长因子β(TGFbeta)。 潜伏的HSV-1病毒的重新激活。

Herpes simplex virus (HSV) infections consist of several distinct stages; namely a primary infection, a latent infection and a reactivation of latent virus producing recurrent disease. In HSV infections of the mouth (herpes labialis), the trigeminal ganglion serves as the site of latent infection. Since a large portion of the population is estimated to have latent HSV infections and since recurrent infections probably represent the largest reservoir of HSV, efforts to control viral reactivation and therefore recurrent infections are extremely important in controlling the spread of the virus in the population. The exact mechanism(s) of HSV latency and reactivation including the roles of the immune, nervous and endocrine systems are largely unknown. Studies designed to unravel the interactions and roles of these different systems in viral reactivation from within the trigeminal ganglia are required before effective intervention can be designed. The single most important tool needed to study HSV reactivation is a good animal model, which unfortunately, does not currently exist. The primary goal of this research proposal is to establish an animal model system for the reactivation of latent HSV-1 from the trigeminal ganglia of mice. Using a well established mouse corneal model for HSV latency, viral reactivation will be achieved using a variety of stressors including infection with mouse hepatitis virus or salmonella typhimurium; use of the immuno-suppressive drugs cyclophosphamide and cyclosporin A; general anesthesia; and exposure to sub-erythemal doses of ultra-violet irradiation. Viral reactivation will be detected by monitoring HSV- specific immunoglobulins, cytotoxic T-cell activity, isolation of infectious virus and the presence of HSV-specific proteins in mouse tissues. Using this model system, additional studies will be performed to analyze the role of immune T cells, and the cytokines interleukin-1 (IL1), IL2, IL6, tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), and transformed growth factor beta (TGFbeta) in the reactivation of latent HSV-1 virus.